Most (maybe all?) species that reproduce sexually have either genders (anisogamy) or mating types (isogamy). There exist today many different type of sexual determination system. There is a whole complicated continuum from species where the gender is exclusively determined genetically (genetic determination system, GSD) to those where the gender is determined by the environment (environment determination system, ESD).
Knowing that genders (and mating types) evolved several independently, what seem to be the ancestral states of sex determination system? Where the first sexually reproducing lineages GSD or ESD? Does it differ between lineages?
Geneticists make new discovery about how a baby's sex is determined
Medical researchers at Melbourne's Murdoch Children's Research Institute have made a new discovery about how a baby's sex is determined -- it's not just about the X-Y chromosomes, but involves a 'regulator' that increases or decreases the activity of genes which decide if we become male or female.
The study, 'Human Sex Reversal is caused by Duplication or Deletion of Core Enhancers Upstream of SOX9' has been published in the journal Nature Communications. MCRI researcher and Hudson Institute PhD student, Brittany Croft, is the first author.
"The sex of a baby is determined by its chromosome make-up at conception. An embryo with two X chromosomes will become a girl, while an embryo with an X-Y combination results in a boy," Ms Croft said.
"The Y chromosome carries a critical gene, called SRY, which acts on another gene called SOX9 to start the development of testes in the embryo. High levels of the SOX9 gene are needed for normal testis development.
"However, if there is some disruption to SOX9 activity and only low levels are present, a testis will not develop resulting in a baby with a disorder of sex development."
Lead author of the study, Professor Andrew Sinclair, said that 90 percent of human DNA is made up of so called 'junk DNA or dark matter' which contains no genes but does carry important regulators that increase or decrease gene activity.
"These regulatory segments of DNA are called enhancers," he said. If these enhancers that control testis genes are disrupted it may lead to a baby being born with a disorder of sex development."
Professor Sinclair, who is also a member of the Paediatrics Department of the University of Melbourne, said this study sought to understand how the SOX9 gene was regulated by enhancers and whether disruption of the enhancers would result in disorders of sex development.
"We discovered three enhancers that, together ensure the SOX9 gene is turned on to a high level in an XY embryo, leading to normal testis and male development," he said.
"Importantly, we identified XX patients who would normally have ovaries and be female but carried extra copies of these enhancers, (high levels of SOX9) and instead developed testes. In addition, we found XY patients who had lost these SOX9 enhancers, (low levels of SOX9) and developed ovaries instead of testes."
Ms Croft said human sex reversal such as seen in these cases is caused by gain or loss of these vital enhancers that regulate the SOX9 gene consequently, these three enhancers are required for normal testes and male development."
"This study is significant because in the past researchers have only looked at genes to diagnose these patients, but we have shown you need to look outside the genes to the enhancers," Ms Croft said.
Professor Sinclair said that across the human genome there were about one million enhancers controlling about 22,000 genes.
"These enhancers lie on the DNA but outside genes, in regions previously referred to as junk DNA or dark matter," he said. "The key to diagnosing many disorders may be found in these enhancers which hide in the poorly understood dark matter of our DNA."
This work was supported by a National Health and Medical Research Council (NHMRC) Program grant 1074258 to Andrew Sinclair, Peter Koopman, Vincent Harley and an NHMRC Project grant 1031214 to Andrew Sinclair.
ARC grants DP150102120 and DP160104948 to Peter Koopman. Brittany Croft was supported by an Australian. Government Research Training Program Scholarship. Rajini Sreenivasan was supported by NHMRC Early 608 Career Fellowship No.1126995. NHMRC Fellowships supported Andrew Sinclair (1062854), Peter Koopman (1059006) and Vincent Harley (1020034) .
Sex Determination: 3 Basic Types of Sex Determination Processes
Homologous chromosomes are pairs of identical chromosomes with similar gene loci carrying similar or different alleles.
Image Courtesy : microbix.com/wp-content/uploads/2011/07/Sex-Determination.jpg
They occur in somatic cells of animals and vascular plants which possess diploid number of chromosomes. Out of the two homologous chromosomes present in an individual, one is derived from the father parent and the other from the mother parent. The two homologous chromosomes of each type do not occur attached to each other in the nucleus of the cell. They come together only during prophase and metaphase of meiosis I.
Genomes (Gk. genos- offspring):
Genome is the complete but single set of chromosomes as found in gametes or gametophyte cells where each chromosome (as well as each gene) is represented singly. The condition of having a single genome or set of chromosomes is called monoploid (Gk. monos- single, aplos- one fold, eidos- form). It is briefly written as In. The somatic or body cells of animals and higher plants generally possess two genomes or two sets of chromosomes.
The condition is called diploid (2n). Several modern day crop plants have more than two sets of chromosomes in their somatic cells, viz. triploid (3n, e.g., Banana), tetraploid (4n, e.g., Rice), hexaploid (6n, e.g., Wheat). The condition of having more than two genomes or sets of chromosomes is known as polyploidy. It is quite common in ferns and mosses. Polyploidy seems to be causative agent of large number of chromosomes present in some organisms, e.g., Amoeba proteus (250), Ophioglossum (Adder’s Tongue Fern, 1262), Geometrid Moth (224).
Gametes possess half the number of chromosomes found in zygote and the cells derived from it. The condition of having half the number of chromosomes is called haploid (Gk. haplos- simple, eidos- form). The gametic number of chromosomes is typically monoploid (In) but in polyploid forms, it is more than monoploid, e.g., 2n, 3n. In order to avoid confusion in this regard the gametic and zygotic conditions are provided with separate symbols of x and 2x.
The somatic cells of several protists, algae and fungi have haploid number of chromosomes. Doubling of chromosomes occurs in the zygote but meiosis occurs in it to restore haploid condition. Male Honey Bee is also haploid because it develops parthenogenetically from an unfertilized egg. The female bee is diploid.
Sex Chromosomes and Autosomes:
Sex chromosomes are those chromosomes which singly or in pair determine the sex of the individual in dioecious or unisexual organisms. They are called allosomes (Gk. alios- other, soma- body) or idiochromosomes (Gk. idios- distinct, chroma- colour, soma- body). A sex chromosome that determines male sex is termed androsome (Gk. ander- male, soma- body), e.g., Y-chromosome in humans.
The normal chromosomes, other than the sex chromosomes if present, of an individual are known as autosomes. Sex chromosomes may be similar in one sex and dissimilar in the other. The two conditions are respectively called homomorphic (= similar, e.g., XX, ZZ) and heteromorphic (= dissimilar, e.g., XY, ZW).
Individuals having homomorphic sex chromosomes produce only one type of gametes. They are, therefore, called homogametic (e.g., human female). Individuals having heteromorphic sex chromosomes produce two types of gametes (e.g., X and Y containing). They are termed as heterogametic (e.g., human male).
Basis of Sex Determination:
Establishment of male and female individuals or male and female organs of an individual is called sex determination. It is of three types— environmental, genic and chromosomal.
A. Environmental or Non-genetic Determination of Sex:
1. Marine mollusc Crepidula becomes female if reared alone. In company of a female, it develops into male (Coe, 1943).
2. Marine worm Bonellia develops into 3 cm long female if its larva settles down in an isolated place. It grows into small (0.3 cm long) parasitic male if it comes closer to an already established female (Baltzer, 1935). The male enters the body of the female and stays there as a parasite.
3. Ophryortocha is male in the young state and female later on.
4. In Crocodiles and some lizards high temperature induces maleness and low temperature femaleness. In turtles, males are predominant below 28°C, females above 33°C and equal number of the two sexes between 28-33°C.
B. Nonallosomic Genic Determination of Sex:
In bacteria, fertility factor present in a plasmid determines sex. Chlamydomonas possesses sex determining genes. Maize possesses separate genes for development of tassel (male inflorescence) and cob (female inflorescence).
C. Chromosomal Determination of Sex:
Henking (1891) discovered an X-body in 50% of the sperms of firefly. Y-body was discovered by Stevens (1902). McClung (1902) observed 24 chromosomes in female Grasshopper and 23 chromosomes in male Grasshopper. Wilson and Stevens (1905) put forward chromosome theory of sex and named the X- and Y- bodies as sex chromosomes, X and Y.
Chromosomal or allosomic determination of sex is based on heterogamesis or occurrence of two types of gametes in one of the two sexes. Male heterogamety or digamety is found in allosome complements XX-XY and XX-X0. Female heterogamety or digamety occurs in allosome complements ZW-ZZ and Z0-ZZ. Sex is determined by number of genomes in haplodiploidy. Chromosomal determination of sex is of the following types:
1. XX—XY Type:
In most insects including fruitfly Drosophila and mammals including human beings the females possess two homomorphic (= isomorphic) sex chromosomes, named XX. The males contain two het- eromorphic sex chromosomes, i.e., XY. The Y-chromosome is often shorter and heterochromatic (made of heterochromatin). It may be hooked (e.g., Drosophila). Despite differences in morphology, the XY chromosomes synapse during zygotene. It is because they have two parts, homologous and differential.
Homologous regions of the two help in pairing. They carry same genes which may have different alleles. Such genes present on both X and Y chromosomes are XY-linked genes. They are inherited like autosomal genes, e.g., xeroderma pigmentosum, epidermolysis bullosa. The differential region of Y-chromosome carries only Y-linked or holandric genes, e.g., testis determining factor (TDF).
It is perhaps the smallest gene occupying only 14 base pairs. Other holandric genes are of hypertrichosis (excessive hairiness) on pinna, porcupine skin, keratoderma dissipatum (thickened skin of hands and feet) and webbed toes. Holandric genes are directly inherited by a son from his father.
Genes present on the differential region of X-chromosome also find expression in males whether they are dominant or recessive, e.g., red-green colour blindness, haemophilia. It is because the males are hemizygous for these genes.
Human beings have 22 pairs of autosomes and one pair of sex chromosomes. All the ova formed by female are similar in their chromosome type (22 + X). Therefore, females are homogametic. The male gametes or sperms produced by human males are of two types, (22 + X) and (22 + Y). Human males are therefore, heterogametic (male digamety or male heterogamety).
Sex of Offspring (Fig. 5.23):
Sex of the offspring is determined at the time of fertilization. It cannot be changed later on. It is also not dependent on any characteristic of the female parent because the latter is homogametic and produces only one type of eggs (22 + X), the male gametes are of two types, androsperms (22 + Y) and gynosperms (22 + X). They are produced in equal proportion.
Fertilization of the egg (22 + X) with a gynosperm (22 + X) will produce a female child (44 + XX) while fertilization with an androsperm (22 + Y) gives rise to male child (44 + XY). As the two types of sperms are produced in equal proportions, there are equal chances of getting a male or female child in a particular mating. As Y-chromosome determines the male sex of the individual, it is also called androsome.
In human beings, TDF gene of Y-chromosome brings about differentiation of embryonic gonads into testes. Testes produce testosterone that helps in development of male reproductive tract. In the absence of TDF, gonads differentiate into ovaries after sixth week of embryonic development. It is followed by formation of female reproductive tract. Female sex is, therefore, a default sex.
2. XX—X0 Types:
In roundworms and some insects (true bugs, grasshoppers, cockroaches), the females have two sex chromosomes, XX, while the males have only one sex chromosome, X. There is no second sex chromosome. Therefore, the males are designated as X0. The females are homogametic because they produce only one type of eggs (A+X).
The males are heterogametic with half the male gametes (gynosperms) carrying X-chromo- some (A+X) while the other half (androsperms) being devoid of it (A + 0). The sex ratio produced in the progeny is 1: 1 (Fig. 5.24).
3. ZW—ZZ Type (= WZ—WW Type).
In birds and some reptiles both the sexes possess two sex chromosomes but unlike human beings the females contain heteromorphic sex chromosomes (AA + ZW) while the males have homomorphic sex chromosomes (AA + ZZ). Because of having heteromorphic sex chromosomes, the females are heterogametic (female heterogamety) and produce two types of eggs, (A + Z) and (A + W). The male gametes or sperms are of one type (A + Z). 1: 1 sex ratio is produced in the offspring (Fig. 5.25).
4. ZO — ZZ Type:
This type of sex determination occurs in some butterflies and moths. It is exactly opposite the condition found in cockroaches and grasshoppers. Here the females have odd sex chromosome (AA + Z) while the males have two homomorphic sex chromosomes (AA + ZZ). The females are heterogametic.
They produce two types of eggs, male forming with one sex chromosome (A + Z) and female forming without the sex chromosome (A + 0). The males are homogametic, forming similar types of sperms (A + Z). The two sexes are obtained in the progeny in 50 : 50 ratio (Fig. 5.26) as both the types of eggs are produced in equal ratio.
It is a type of sex determination in which the male is haploid while the female is diploid. Haplodiploidy occurs in some insects like bees, ants and wasps. Male insects are haploid because they develop partheno-genetically from unfertilized eggs. The phenomenon is called arrhenotoky or arrhenotokous parthenogenesis. Meiosis does not occur during the formation of sperms.
Females grow from fertilized eggs and are hence diploid. Queen Bee picks up all the sperms from the drone during nuptial flight and stores the same in her seminal vesicle. Formation of worker bees (diploid females) and drones (haploid males) depends upon the brood cells visited by the queen. While visiting the smaller brood cells, the queen emits sperms from its seminal receptacle after laying the eggs.
As it visits the larger brood cells, it lays the eggs but the seminal receptacles fail to emit the sperms due to some sort of pressure on the ducts coming out of them. When a queen is to be formed the workers enlarge one of a small brood cell having fertilized egg and feed the emerging larva on a rich diet.
Males are normally fertile haploids due to development from unfertilized eggs. Occasionally diploid infertile males are also produced from heterozygous females through fertilization.
The Embryo Project Encyclopedia
The Sex-determining Region Y (Sry in mammals but SRY in humans) is a gene found on Y chromosomes that leads to the development of male phenotypes, such as testes. The Sry gene, located on the short branch of the Y chromosome, initiates male embryonic development in the XY sex determination system. The Sry gene follows the central dogma of molecular biology the DNA encoding the gene is transcribed into messenger RNA, which then produces a single Sry protein. The Sry protein is also called the testis-determining factor (TDF), a protein that initiates male development in humans, placental mammals, and marsupials. The Sry protein is a transcription factor that can bind to regions of testis-specific DNA, bending specific DNA and activating or enhancing its abilities to promote testis formation, marking the first step towards male, rather than female, development in the embryo.
In humans the first step in the development of an organism's sex is the inheritance of an X chromosome from the mother, and either an X or Y chromosome from the father. Typically, an XX individual develops as a female and an XY individual develops as a male. Studies by University of Kansas zoologist Clarence Erwin McClung in Lawrence, Kansas at the turn of the twentieth century helped researchers focus on the roles of chromosomes for sex determination. McClung theorized that there were two distinct types of spermatozoa, each of which resulted in different forms of fertilized eggs, leading to either male or female development. Nettie Maria Stevens, a post-doctorate researcher at Bryn Mawr College, located near Philadelphia, Pennsylvania, expanded upon McClung's theory in 1905, observing that spermatozoa are of two distinct forms, containing either an X or a Y chromosome. Based upon her research on sex determination in insect species, Stevens concluded that the Y chromosome carries the genetic material that leads to male development.
Stevens's work identified the Y chromosome as a heritable structure that somehow caused sex determination in the embryo. Her results supported the theory proposed in the early 1890s by zoologist researcher Walter Sutton at Columbia University in New York City, New York and biologist Theodore Boveri at University of Würzburg in Würzburg, Germany, that chromosomes contain genetic material. At that time, however, researchers couldn't detail the mechanism through which chromosomes work to induce changes in the cell. Experiments conducted by Frederick Griffith in 1928 at the Ministry of Health in London, England confirmed the existence of a factor in cells capable of transferring genetic information.
In 1944 Oswald Avery, Colin Macleod, and Maclyn McCarthy, at the Rockefeller Institute for Medical Research in New York City, New York, discovered that chromosomes contain DNA, the molecule that encodes an organism’s genetic information. The discovery of DNA's structure in 1953 by James Watson and Francis Crick at the Cavendish Laboratory in Cambridge, UK enabled researchers to develop biochemical technologies, such as Polymerase Chain Reaction, which can replicate a single DNA sequence several million times. These techniques enabled researchers to describe the mechanisms that underlie developmental pathways, including the role of SRY gene in sex determination.
Starting in the early 1980s, research teams in London, UK led by Robin Lovell-Badge at the National Institute for Medical Research and Peter Goodfellow at the Cancer Research UK London Research Institute sought to identify the genes present on the Y chromosome that induced male development. Scientists first scanned the Y chromosomes of several mammals for the presence of genes involved in testis formation. The scientists claimed that the gene would encode for the testis-determining factor (TDF), a protein responsible for causing testis to develop in embryos. The team found a sequence on the Y chromosomes of several species of mammals. The transcripts from those sequences were all found only in testes. The gene, designated the Sex-determining region Y, provided a candidate for expression of the TDF.
Confirmation of the Sry gene encoding the TDF came from several experiments that focused on mutations in the SRY gene. Early evidence came from research conducted by Peter Goodfellow and his teams at both the Cancer Research UK London Research Institute and the National Institute for Medical Research in the late 1980s and early 1990s. That research showed that mutations in the Sry gene halted the embryonic development of testes, resulting in organisms that possessed a Y chromosome but expressed female phenotypic characteristics. Robin Lovell-Badge and her team at the National Institute for Medical Research later confirmed Sry gene's role in sex determination in an experiment where researchers injected Sry gene sequences into chromosomally female (XX) mice embryos during early embryonic development, and the embryos developed into males.
Throughout the 1990s, several researchers argued that Sry protein acted directly upon the genital ridge, the region in early embryonic development from which either the ovary or the testis form. Researchers assumed that Sry protein helped change epithelial cells into Sertoli cells. Sertoli cells are only in males and produce key proteins and hormones during male development. However, later scientists argued that SRY protein indirectly induces mesonephric cells to migrate into the genital ridge. SRY protein causes cells in the genital ridge to secrete a chemotactic factor that causes cells from the adjacent mesonephros to migrate in to the genital ridge. The mesonephric cells, rather than SRY protein directly, induce the genital epithelial cells to become Sertoli cells.
Researchers have linked mutations in the SRY gene to forms of sex reversal. One example is Swyers syndrome, a condition in which a person who has XY sex chromosomes develops the physical characteristics of a female. Mutations in the SRY gene account for between fifteen to twenty percent of cases of Swyers syndrome. Additionally, the presence of SRY gene in genetically XX individuals results in XX male syndrome. This state often results from improper crossing over between X and Y chromosomes during meiosis in the father, resulting in the presence of SRY gene sequences in X chromosomes.
The Y chromosome: beyond gender determination
The human genome is organized into 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), with each parent contributing one chromosome per pair. The X and Y chromosomes, also known as the sex chromosomes, determine the biological sex of an individual: females inherit an X chromosome from the father for a XX genotype, while males inherit a Y chromosome from the father for a XY genotype (mothers only pass on X chromosomes). The presence or absence of the Y chromosome is critical because it contains the genes necessary to override the biological default - female development - and cause the development of the male reproductive system.
Although the Y chromosome's role in sex determination is clear, research has shown that it is undergoing rapid evolutionary deterioration. Many generations ago the Y chromosome was large, and contained as many genes as the X chromosome. Now it is a fraction of its past size and contains fewer than 80 functional genes. This has led to debates and concerns over the years regarding the Y chromosome's eventual destiny. Many speculate that the Y chromosome has become superfluous and could completely decay within the next 10 million years. While studies of the Y chromosome have been challenging due to the palindromic and repeat-rich nature of its DNA sequence, recent genomic advances have provided some unexpected insights.
This installment of the Genome Advance of the Month highlights two studies published in the April 24, 2014, issue of Nature that explore the evolutionary path of the Y chromosome in various mammals. Together, these studies demonstrate the stability of the Y chromosome over the past 25 million years. They further reveal some critical functions of the Y chromosome that suggest it may be here to stay.
To get started, let's first delve into the evolutionary origin of the sex chromosomes, roughly 200-300 million years ago. The X and Y chromosomes, both of which derived from autosomes, were initially about the same size. At some specific time along the way, the Y chromosome gradually lost the ability to recombine - or exchange genetic information - with the X chromosome and began to evolve independently. This quickly led to a catastrophic deterioration of the Y chromosome, which now contains only 3 percent of the genes that it once shared with the X chromosome.
Recent work from the research groups of David C. Page, M.D., at the Whitehead Institute, Massachusetts Institute of Technology, and Henrik Kaessmann, Ph.D., at the Swiss Institute of Bioinformatics and the University of Lausanne in Switzerland, suggests that the initially rapid decline of the Y chromosome may have leveled off and stabilized.
Using different genomic technologies, these two research teams analyzed the evolution of the Y chromosome independently in two separate sets of mammals that covered more than 15 different species, including humans, chimpanzees, rhesus monkeys, bulls, marmosets, mice, rats, dogs and opossums. Strikingly, they found a small but stable group of essential regulatory genes on the Y chromosome that have endured over a long evolutionary period of time, even while surrounding genes were decaying. Significantly, these genes play a critically important role in governing the expression of other genes throughout the genome and may affect tissues throughout the human body. One of the reasons for the continued endurance of these regulatory Y chromosome genes is that they are "dosage-dependent," meaning that two copies are required for normal function.
For most genes on the X-chromosome, only one copy is required. Females have two X chromosomes and therefore two copies of every X-linked gene, so one copy is randomly inactivated, or turned off. Males have only one X chromosome and therefore only one copy is expressed.
However, regulatory genes are often dosage-dependent and haplo-insufficient, i.e., two copies of the gene are required and the presence of only one copy can lead to abnormalities or disease. In females, these regulatory genes escape X-inactivation so that the copy on the second X chromosome is also expressed in males, who only have one X chromosome, the preservation of this group of regulatory genes on the Y chromosome is crucial for providing the second copy.
Overall, what this means is that beyond its role in sex determination and fertility, the Y chromosome also contains important genes that are critical for the health and survival of males.
These findings have considerable implications for our understanding of differences in biology, health and disease between men and women. Because genes on the X and Y chromosomes have a history of selection independent of each other, subtle functional differences may exist that are a direct consequence of genetic differences on the two chromosomes. While these differences have not yet been explored in great detail, more studies on the conserved Y chromosome genes can help us to understand differences in the basic biology and susceptibility to diseases in men and women and better guide health management.
Read the articles:
Bellott DW, Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Cho TJ, Koutseva N, Zaghlul S, Graves T, Rock S, Kremitzki C, Fulton RS, Dugan S, Ding Y, Morton D, Khan Z, Lewis L, Buhay C, Wang Q, Watt J, Holder M, Lee S, Nazareth L, Rozen S, Muzny DM, Warren WC, Gibbs RA, Wilson RK, Page DC. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature, 508(7497):494-9. 2014. [PubMed]
Cortez D, Marin R, Toledo-Flores D, Froidevaux L, Liechti A, Waters PD, Grützner F, Kaessmann H. Origins and functional evolution of Y chromosomes across mammals. Nature, 508(7497):488-93. 2014. [PubMed]
Choosing a sex
Since Janet and Dr Devore were born there is much more understanding about Disorders of Sex Development.
Today the whole family of children born with a DSD are involved from the beginning, and urology, endocrinology, genetics, social work and psychology experts also work together.
For a child born of indeterminate sex they will undergo number of tests including those involving chromosomes, hormones and internal organs. To further complicate things the test results are not just either male or female, they can be on a sliding scale between the two.
Ultimately the sex chosen for an intersex baby is the one doctors and their family believe they will grow up to identify with best.
Dr Devore and Janet were both born at a time when parents went along with what the doctors said and surgery was seen as the first thing to do.
They have both had multiple operations. Dr Devore has had 20 surgeries, the first at three months old.
"In my view all the surgeries I suffered up to age 19 were unnecessary failures," he says.
"I lost a tremendous amount of feeling tissue that I would like to have."
Some people now believe that surgery should be left until the child can make the decision themselves.
"There are a lot of activists that describe infant surgery in one word - mutilation," explains Dr Devore.
"Unless there's a medical necessity to change the appearance of those genitals I don't think they should be cut on at all," he asserts.
"It's the kid's genitals, not the parents or the doctors and when they're young adults they are going to want them to work."
But Tom Kolon, MD Urologist at the Children's Hospital of Philadelphia points out there can be a problem with leaving it until the child has grown up.
"I think we would all want the child to be able to make the decisions themselves. The problem there is if you wait until they are old enough and mature enough to understand and say yes - have you hurt them by not doing the surgery or the medication earlier?"
On April 24, 2018, a suspect in California’s notorious Golden State Killer cases was arrested after decades of eluding the police. The capture of Joseph James DeAngelo, a former police officer, was a critical step toward closing the books on 12 unsolved murders and at least 45 rapes that were committed throughout California from 1976 to 1986 . While DeAngelo’s arrest was widely celebrated, concerns linger regarding the forensic techniques that ultimately brought him to justice. That is because the police identified DeAngelo by first identifying his relatives using a free, online genetic database populated by individuals researching their family trees. By participating in genetic genealogy databases and using other personal genetic services intended to facilitate self-discovery, individuals can become criminal informants vis-à-vis their own families. But should this be allowed?
Department of Evolution, Ecology, & Organismal Biology Colloquium
see schedule at BIOL 252 Seminars
Thursdays at 4:10, Genomics Auditorium
Evolution, Ecology, and Organismal Biology Graduate Program Seminar
see schedule at EEOB 265 Lunch Bunch
Fridays at noon, normally in 2200 Spieth Hall
Genetics, Genomics and Bioinformatics (GGB) Graduate Program Seminar
see schedule at BIOL/GGB 261
Wednesdays at 12:10
Neuroscience Seminar Series
see schedule at NRSC 287
Tuesdays at 4pm Genomics Auditorium
The MCB Department is divided into five Divisions that reflect general research areas. Department committees with representatives from each of the Divisions offer the basis for governance, oversight of graduate affairs, overall curriculum, facilities, and such. However, each Division is in charge of its own course offerings, seminar series and annual retreat.
- Biochemistry, Biophysics and Structural Biology
- Cell & Developmental Biology
- Genetics, Genomics and Development
- Immunology and Pathogenesis
Biochemistry, Biophysics and Structural Biology
Faculty of the Division of Biochemistry, Biophysics and Structural Biology (BBS) are engaged in advanced study of the biological chemistry of cellular metabolites enzymatic catalysis the structure and function of biological macromolecules, especially nucleic acids and proteins the supramolecular organization of complex cellular assemblies, including the transcription and DNA replication proteins, biological membranes and, regulation of biological processes such as chromosomal folding, protein secretion and intracellular signaling. These problems are being investigated in systems that range from bacteria and bacteriophage to yeast to human cells and their viruses. Faculty of this division also participate in interdepartmental programs in structural biology, chemical biology, microbiology and toxicology. Facilities include those for protein-sequence analysis, peptide and oligonucleotide synthesis, access to the synchrotron at Lawrence Berkeley National Lab for X-ray crystallography, and NMR spectrometry. The Division holds a weekly seminar series by invited speakers, and each year is the host for the Chiron, Li, Stanier, and Wilson Lecturers. The Division holds its annual retreat at the Asilomar Conference Center in Pacific Grove, California, in early January.
Cell & Developmental Biology
Faculty of the Division of Cell & Developmental Biology (CDB) pursue research aimed at detailed understanding of: the structure and function of cellular components, such as membranes, organelles, chromosomes and the cytoskeleton cellular processes, such as epithelial transport, cell motility, mitosis, protein targeting and secretion, stem cell plasticity, and eukaryotic cell cycle control tumor biology cellular physiology the origin of cell polarity and the molecular and cellular basis for axis formation, morphogenetic movements, fate determination, and gene regulation during embryogenesis and cellular differentiation. These issues are being addressed in systems as diverse as yeast, fruit flies, worms, sea urchins, frogs, mice and mammalian cells in culture, and these studies exploit techniques ranging from molecular biology and microinjection to digital imaging and mathematical modeling. Specialized equipment for confocal fluorescence microscopy, video imaging, and computer simulations are available in shared core facilities in the Life Sciences Addition where many of the faculty are housed. The Division sponsors a weekly seminar series by invited speakers, holds informal journal clubs on topics in cell biology and holds its annual retreat at the Granlibakken Conference Center in Lake Tahoe, California, in the Fall Semester.
Genetics, Genomics and Development
Faculty of the Division of Genetics, Genomics and Development (GGD) explore the fundamental mechanisms of genetics, evolution, and development using genetic, molecular, biochemical, computational, and genomic approaches. Interests include the basic mechanisms of transcription, RNA processing, and translation, and their control structure, function, and evolution of gene regulatory networks origin and evolution of animal signaling and patterning mechanisms in development replication, structure, dynamics, and evolution of genomes embryonic pattern formation and morphogenesis, including the control of cell fate regulatory mechanisms at the genomic level, including sex determination and dosage compensation genetic and genomic diversity and variation within natural and artificial populations. GGD research groups take advantage of a wide variety of organisms to address these issues, including both established model systems (e.g., yeast, nematodes, frult flies, zebrafish), and new genome-enabled emerging models (e.g., sea squirts, sea anemones, frogs, choanoflagellates). The Division is home to the Center for Integrative Genomics and participates in the campus-wide Computational Biology Initiative. It also has close ties with major genome sequencing initiatives including the Drosophilia genome project and numerous animal and fungal genome projects at the nearby DOE Joint Genome Institute (JGI) in Walnut Creek and elsewhere, as well as associated research at the Gump Field Station in Moorea, French Polynesia. The Division sponsors a weekly seminar series by invited speakers and holds its annual retreat at the Granlibakken Conference Center in Lake Tahoe, California, in the early fall.
Immunology and Pathogenesis
Faculty of the Division of Immunology and Pathogenesis (I&P) conduct advanced research to understand the mouse and human immune system. Various division members are interested in the structure and function of cell surface receptors, the assembly of antigen receptor genes, and other aspects of immune recognition. In addition, we focus upon immune surveillance in cancer, apoptosis, tissue transplantation, autoimmunity and infectious disease. The faculty offers a cohesive program of training in modern molecular and cellular immunology that contributes to and benefits from its close ties to research in the allied fields of biochemistry, molecular and cell biology, cell biology and genetics being conducted in other Divisions. The Division, in conjunction with the Cancer Research Laboratory, supervises and maintains state-of-the-art instrumentation for advanced microscopy, flow cytometry, and the construction of transgenic and gene-targeted mice. The Division sponsors a weekly seminar series by eminent immunologists, and jointly holds its annual retreat with the immunology program at the University of California, San Francisco.
Faculty in the Division of Neurobiology (NEU) engage in advanced research in neuroscience from the molecular to the integrative and computational levels. Specific topics under investigation include: molecular and biophysical analysis of ion channels receptors and signal transduction mechanisms formation and plasticity of synapses control of neural cell fate and pattern formation neuronal growth-cone guidance, target recognition and regeneration mechanisms of sensory processing in the visual, auditory, olfactory and gustatory systems and development and function of neural networks. The preparations being investigated range from cells in culture, to simple invertebrate systems and model genetic organisms, to the mammalian cerebral cortex. The faculty offer an integrated approach to training in modern neurobiology, spanning the use of molecular and classical genetics molecular, biochemical, cell biological and anatomical methods electrophysiological and biophysical techniques functional genomics advanced optical imaging and computational analysis. Members of the Division (as well as faculty from the Divisions of Cell & Developmental Biology and Genetics & Development) also participate in the campus-wide Neuroscience Graduate Program, which is administered by the Helen Wills Neuroscience Institute and includes faculty from the Departments of Psychology, Integrative Biology, Physics (College of Letters and Science), Vision Science (School of Optometry), Environmental Science, Policy and Management (College of Natural Resources), and Chemical Engineering (College of Chemistry). While the MCB Program welcomes students interested in all areas of neuroscience, students focused primarily on systems-level and cognitive neuroscience are also encouraged to consider applying to the Neuroscience Graduate Program. The Division sponsors a weekly seminar series by invited speakers, and together with the Helen Wills Neuroscience Institute co-sponsors the annual campus-wide Neuroscience retreat.
Advancing Health Equity by Addressing the Social Determinants of Health in Family Medicine (Position Paper)
Social determinants of health (SDoH) are the conditions under which people are born, grow, live, work, and age, and include factors such as socioeconomic status, education, employment, social support networks, and neighborhood characteristics. 1 These have a greater impact on population health than factors like biology, behavior, and health care. 2,3 SDoH, especially poverty, structural racism, and discrimination, are the primary drivers of health inequities. 4-6 Reducing health inequities is important because they are pervasive unfair and unjust individuals affected have little control over the contributing circumstances affect everyone and can be avoided with existing policy solutions. 7
The purpose of this position paper is to outline prevalent health inequities describe how social factors impact health discuss the role family physicians can play in addressing SDoH and reducing health inequities and state the American Academy of Family Physicians (AAFP) stance on relevant policy interventions.
Social Determinants of Health: The conditions under which people are born, grow, live, work, and age. 1
Structural Determinants of Health Inequities: The social, economic, and political mechanisms which generate social class inequalities in society. 8
Health Equity: “Health equity means that everyone has a fair and just opportunity to be as healthy as possible. This requires removing obstacles to health such as poverty, discrimination, and their consequences, including powerlessness and lack of access to good jobs with fair pay, quality education and housing, safe environments, and health care.” 9
Health Disparities: “A type of difference in health that is closely linked with social or economic disadvantage. Health disparities negatively affect groups of people who have systematically experienced greater social or economic obstacles to health. These obstacles stem from characteristics historically linked to discrimination or exclusion such as race or ethnicity, religion, socioeconomic status, gender, mental health, sexual orientation, or geographic location. Other characteristics include cognitive, sensory, or physical disability.” 10
Health Inequities: “A difference or disparity in health outcomes that is systematic, avoidable, and unjust.” 10
The most prevalent and severe health inequities occur where there is poverty, systematic racism, and discrimination. 6 Some of the most common and well-researched health inequities are experienced between groups based on socioeconomic status, race and ethnicity, sexual orientation and gender expression, as well as geographic location. 11,12 Information is provided in the following sections to help characterize these health inequities. However, this is not intended to be comprehensive or cover all health inequities.
Socioeconomic status refers to the social and economic factors that influence the position individuals hold in society. This includes factors like occupation, class, education, income, and wealth. 11,12 Individuals with higher socioeconomic status consistently experience better health outcomes than those with lower socioeconomic status, and this occurs across a social gradient. 11 It is not just the very poor who are affected. Research has shown that:
- Nearly as many deaths are caused by social factors as by behavioral or pathophysiological factors. 13,14 One group of researchers found that in the year 2000, more than 244,000 deaths could be attributed to low education (less than some college education) more than 133,000 deaths could be attributed to individual poverty (household annual income of ≤$10,000) and more than 39,000 deaths could be attributed to area poverty (live in a county where ≥20% of the population lives below the poverty line). 13
- The death rate in 2007 was more than 2.5 times greater for individuals without a high school diploma compared to those with at least some college, and the disparity had increased since 1989. 15
- Income inequality is associated with greater health care expenditures, health care use, 16 and death from cardiovascular disease and suicide. 17
Race, Ethnicity, and Discrimination
Race and ethnicity are associated with many indicators of health status, even after considering socioeconomic status, behavior, and other characteristics. Systematic, persistent, and long-felt discrimination is thought to be the main contributor. 11 Research has shown that:
- Life expectancy is consistently lower for non-Hispanic black individuals compared to non-Hispanic white and Hispanic individuals of the same sex (Figure 1). 18
- The infant mortality rate is more than double among infants born to non-Hispanic black women compared to infants born to non-Hispanic white and Hispanic women (Figure 2). 19
- Typical drivers of infant mortality do not fully explain the variation. Research has shown that:
- The infant mortality rate is greater among infants born to non-Hispanic black women across all age groups and all socioeconomic levels. 20
- The infant mortality rate is greater among infants born to non-Hispanic black women across all educational levels, and the disparity increases for those with a master’s degree or higher. In fact, the infant mortality rate is highest for black women with a doctorate or professional degree. 20
- The prevalence of alcohol use during pregnancy is roughly the same among non-Hispanic black and non-Hispanic white women, and non-Hispanic white women are more likely to smoke cigarettes. 20
Sexual Orientation and Gender Expression
Lesbian, gay, bisexual, and transgender (LGBT) people also experience higher levels of discrimination, stigma, stress, and worse outcomes for a variety of health status indicators. Research has shown that:
- All-cause mortality rates were found to be greater among gay men compared to heterosexual men. However, this was driven almost entirely by differences in HIV-related mortality. 21
- Current alcohol use was greater among gay and bisexual men compared to heterosexual men, as well as greater among lesbian women compared to heterosexual women. 22
- Heavy drinking was also greater among lesbian and bisexual women compared to heterosexual women. 22
- Current smoking was greater among gay men and lesbian women compared to heterosexual men and women. 22
- Delaying health care due to cost was greater among gay and bisexual men and lesbian and bisexual women compared to heterosexual men and women. 22
- LGBT individuals are more likely than cisgender or heterosexual people to experience violence, victimization, harassment, and discrimination. 23
Neighborhood and Place
The physical features of an area can impact people’s health. Physical features like air and water quality and climate, as well as housing, parks, and other recreation areas all play a part in physical activity and life expectancy. 11 Research has shown that:
- There is more than a 20-year gap in life expectancy between U.S. counties with the highest and lowest life expectancy and this gap has continued to grow since the 1980s. 24 Life expectancy gaps of up to 25 years have also been identified between different neighborhoods within the same city (Figure 3). 25
- Improving features of the built environment, such as sidewalks and streetscapes, the density of parks, and recreational facilities have been shown to be associated with greater levels of physical activity in children and adults. 26
How Social Factors Impact Health
Health equity scholars use a metaphor of a “stream” of causation to illustrate how social factors impact health. The “downstream” factors include issues that medicine and public health typically deal with—morbidity and mortality, access to health care, behavioral risk factors, and living conditions. The questions that arise from this illustration are why are so many people sick and why are there such great differences among groups? The answer lies in the “upstream” factors, which include governance, culture, and societal values. These, as well as economic, social, and public policies, are the factors that lead to long-held social inequities (Figure 4). 8,27 To understand how social factors impact health, it is important to understand how risk factors are shaped upstream, and how differences in living conditions and exposures are physically embodied by individuals.
Upstream Factors: The Structural Determinants of Health Inequities
The structural determinants of health inequities are the social, economic, and political mechanisms which generate social class inequalities in society. 8 These are macro-level factors that impact large numbers of people. Examples of structural determinants of health include the degree that government subsidizes health care or education decisions about pollution, including minimum standards or where toxic substances are stored or released and decisions about the built environment, which can benefit or harm communities. These all contribute to social class inequalities. Jim Crow laws and redlining are more specific examples. These laws and corporate policies legislated segregation, restricted access to good housing from black Americans, and reduced their ability to influence governmental decisions or live in a healthy neighborhood. This had a substantial negative impact on the health of black Americans. Data showed that life expectancy and infant mortality improved for black Americans after these policies were eliminated. 24,28
Downstream Factors: Opportunities and Constraints to Health Promoting Resources
Social factors also influence health by providing or constraining opportunities for people to access resources that promote better health. Individuals with low socioeconomic status are less likely to be able to acquire health care, nutritious foods, good educational opportunities, safe housing, or safe spaces for exercise. 29 Negative health behaviors, like tobacco, alcohol, or explicit drug use are often pervasive in disadvantaged communities. These types of behaviors are then socially patterned in children, who have not fully developed their ability to make rational decisions. 30 These factors are shaped by more upstream factors.
Chronic Stress and Embodiment
The upstream and downstream factors shape the conditions under which people live. Differences in living conditions and opportunities to make healthy decisions result in differentials in exposures and chronic stress. Embodiment is “a concept referring to how we literally incorporate, biologically, the material and social world in which we live. ” 31 Social factors are embodied as individuals are exposed to repeated and chronic stress. 32 The autonomic nervous system, the hypothalamic-pituitary-adrenal axis, and the cardiovascular, metabolic, and immune systems protect the body by responding to internal and external stress. Over time, chronic stress can increase the allostatic load, or the “wear and tear” that accumulates on the body over time. This “wear and tear” has health damaging effects. 32,33 Historically-disadvantaged groups have been found to experience greater allostatic load, more “wear and tear” than more advantaged groups. 34 Embodiment and allostatic load are thought to explain why social factors are linked with almost every measure of health status throughout time. 31,33
Call to Action
The AAFP urges its members to become more informed about the impact SDoH have on health and health inequities, and to identify tangible next steps they can take to address their patients’ SDoH and reduce health inequities within their scope. The AAFP also urges hospitals and health care systems to consider the SDoH in their strategic plans and to provide their staff, including family physicians, with opportunities to engage with and advocate on behalf of their community to advance health equity. In addition, the AAFP urges health insurers and payors to provide appropriate payment to support health care practices to identify, monitor, assess, and address SDoH. 35 Finally, since health inequities arise outside of the health care sector, the AAFP urges funders, including the federal government, to provide sufficient funding to address the SDoH and reduce health inequities. In addition to other interventions, this includes robust financial support for the nation’s public health infrastructure to support their efforts to facilitate cross-sector community collaboration, strategic planning for health, Health in All Policies, and the core public health functions. 36
The Role of Family Physicians in Reducing Health Inequities
Family physicians can play an important role in addressing both the upstream and downstream SDoH. They provide high-quality health care for underserved populations more so than other medical specialties. 37 Family physicians can also work with their practice teams and community members to address SDoH in any of the following ways:
- Knowing how patients are affected by SDoH and helping address their needs to improve their health.
- Creating a practice culture that values health equity by addressing implicit bias in your practice and using cultural proficiency and health literacy standards.
- Understanding what health inequities exist within your community and helping raise the prominence of these issues among the public and policymakers.
- Knowing which organizations are working to improve health equity in your community and what your community’s health agenda includes.
- Advocating for public policies that address SDoH and reduce health inequities.
The AAFP has created resources to assist family physicians and their health care teams at The EveryONE Project Toolkit.
The AAFP supports the following types of public policies for their ability to address SDoH and reduce health inequities.
- Access to Health Care: The AAFP recognizes that health is a basic human right for every person and that the right to health includes universal access to timely, acceptable, and affordable health care of appropriate quality. 38 All people of the world, regardless of social, economic, or political status, race, religion, gender, or sexual orientation should have access to essential health care services. 39 The AAFP also urges its members to become involved personally in improving the health of people from minority and socioeconomically disadvantaged groups. The AAFP supports: (1) cooperation between family physicians and community health centers to expand access to care (2) regulatory and payment policies that encourage the establishment and success of physician practices in underserved areas (3) programs that encourage the provision of services by physicians and other health care professionals in underserved areas and that meet the unique health needs of those communities and (4) public policies that expand access to care and address SDoH. 40
- Health in All Policies: The AAFP supports adoption of a Health in All Policies strategy by all governing bodies at the local, state, and federal levels. Health in All Policies strategy aims to improve the policymaking process by incorporating health implications, evidence-based information, and community input. This is intended to help inform policymakers about how their decisions about laws, regulations, and policies will impact health and health equity. 41
- Federal Nutrition Programs: The AAFP supports federal nutrition programs as a matter of public health. Access to affordable and healthy food significantly affects an individual’s health, education, and development. 42 Food access also supports medical treatment that requires patients to take medications with food. In 2015, more than 42 million people in the U.S. were living in food insecure households, including more than 13 million children. 43
- Anti-Poverty Programs: The AAFP supports programs that lift people out of poverty and has issued the position paper, Poverty and Health – The Family Medicine Perspective. 44 Poverty has been defined as the inability to acquire goods and services that are viewed as necessary to participate in society and negatively affects almost every indicator of health status. 12,45 The poverty threshold in the U.S. was $12,752 for an individual under age 65 and $25,094 for a family of four in 2017, 46 with 12.3% of individuals in the U.S. considered living in poverty. 47 Examples of policies that are effective at lifting people out of poverty include: the earned income tax credit, Social Security, unemployment insurance, and rental assistance programs. 48,49
- Support for the Homeless: The AAFP supports Housing First programs that offer rapid access to permanent, affordable housing integrated with health care and supportive services. Housing First is a model defined by the U.S. Department of Housing and Urban Development (HUD) as a method to “quickly and successfully connect individuals and families experiencing homelessness to permanent housing without preconditions and barriers to entry. ” Preconditions and barriers can include, but are not limited to sobriety, treatment, or service participation requirements. 50 Housing impacts health care. Access to safe and affordable housing is a SDoH. Homelessness may exacerbate existing health conditions and lead to the development of new health conditions. Persons who are homeless frequently experience co-occurring severe physical, psychiatric, substance use, and social problems. 51 Health care services are more effective when a patient is housed, and maintaining housing is more likely when comprehensive primary health care services are available. Effective strategies to end homelessness must address this complexity of health conditions and disability faced by persons who are homeless.
- Civil Rights and Anti-Discrimination: The AAFP opposes all discrimination in any form, including, but not limited to, that on the basis of actual or perceived race, color, religion, gender, sexual orientation, gender identity, ethnic affiliation, health, age, disability, economic status, body habitus, or national origin. 52
- Educational Achievement: The AAFP supports programs that improve equitable access to high-quality education and equitable educational achievement. Education is associated with many health behaviors, and therefore affect health status. Individuals with lower education are more likely to smoke, have an unhealthy diet, and lack exercise. 53 They also have a lower life expectancy. 54 Despite this, school funding, teacher-to-pupil ratio, and other important indicators of educational quality are not distributed evenly by state and community. 55 All schools should have sufficient funding to meet the educational needs of its students and promote success. Special attention should be paid to inner city and rural schools that are often under-resourced and may need increased resources to meet their students’ needs. Based on strong evidence showing improved educational, social, and health-related outcomes (especially in low-income or racial and ethnic minority communities) the AAFP supports funding for center-based early childhood education, 56 full-day kindergarten, 57 and out-of-school-time academic programs. 58 The AAFP also supports funding for grants, scholarships, and other means of financial support for low-income college students.
- Built Environment: The AAFP supports improvements to the built environment, such as designing walkable neighborhoods, complete streets, and mixed-use zoning as a means to improve community health. 59 The AAFP also supports equitable improvements to the built environment, with a special emphasis on disadvantaged communities, and community input into these decisions to ensure that current residents are not displaced or otherwise negatively impacted. 60
- Home Visitation Programs in Pregnancy and Early Childhood: The AAFP supports home visitation programs in pregnancy and early childhood where trained professionals visit families and provide information and training about health, development, and care of children. These programs offer families the necessary resources and skills to raise children who are physically, socially, and emotionally healthy and ready to learn. 61
- Alternate Payment Models: The AAFP supports alternative payment models that ensure SDoH are appropriately accounted for in the payment and measurement design so that practices have adequate support to improve quality and outcomes for all patients, eliminate health disparities, and reduce costs for the health care system. 35
- Medical Education: The AAFP supports education on SDoH and their impacts on health inequity to be integrated into all levels of medical education. Physicians should be knowledgeable about the impact of SDoH and have the ability to work with patients to address SDoH by tailoring treatment to address patients’ barriers to better health. 62
Social determinants of health have a substantial impact on the health of many Americans and are a key driver of health inequities. Family physicians have an important role in addressing both upstream and downstream SDoH and reducing health inequities by providing high-quality health care for the underserved and advocating to raise the prominence of health inequities among the public and policymakers. The AAFP urges its members to work with their practice teams and community members to address SDoH and urges government, health care systems, and public health organizations to develop policies and practices that address SDoH to help reduce health inequities.
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