The use of race, ethnicity and ancestry in human genetic research

Post-Human Genome Project progress has enabled a new wave of population genetic research, and intensified controversy over the use of race/ethnicity in this work. At the same time, the development of methods for inferring genetic ancestry offers more empirical means of assigning group labels. Here, we provide a systematic analysis of the use of race/ethnicity and ancestry in current genetic research. We base our analysis on key published recommendations for the use and reporting of race/ethnicity which advise that researchers: explain why the terms/categories were used and how they were measured, carefully define them, and apply them consistently. We studied 170 population genetic research articles from high impact journals, published 2008-2009. A comparative perspective was obtained by aligning study metrics with similar research from articles published 2001-2004. Our analysis indicates a marked improvement in compliance with some of the recommendations/guidelines for the use of race/ethnicity over time, while showing that important shortfalls still remain: no article using 'race', 'ethnicity' or 'ancestry' defined or discussed the meaning of these concepts in context; a third of articles still do not provide a rationale for their use, with those using 'ancestry' being the least likely to do so. Further, no article discussed potential socio-ethical implications of the reported research. As such, there remains a clear imperative for highlighting the importance of consistent and comprehensive reporting on human populations to the genetics/genomics community globally, to generate explicit guidelines for the uses of ancestry and genetic ancestry, and importantly, to ensure that guidelines are followed.     

Comparing genetic ancestry and self-reported race/ethnicity in a multiethnic population in New York City

Self-reported race/ethnicity is frequently used in epidemiological studies to assess an individual’s background origin. However, in admixed populations such as Hispanic, self-reported race/ethnicity may not accurately represent them genetically because they are admixed with European, African and Native American ancestry. We estimated the proportions of genetic admixture in an ethnically diverse population of 396 mothers and 188 of their children with 35 ancestry informative markers (AIMs) using the STRUCTURE version 2.2 program. The majority of the markers showed significant deviation from Hardy-Weinberg equilibrium in our study population. In mothers self-identified as Black and White, the imputed ancestry proportions were 77.6% African and 75.1% European respectively, while the racial composition among self-identified Hispanics was 29.2% European, 26.0% African, and 44.8% Native American. We also investigated the utility of AIMs by showing the improved fitness of models in paraoxanase-1 genotype-phenotype associations after incorporating AIMs; however, the improvement was moderate at best. In summary, a minimal set of 35 AIMs is sufficient to detect population stratification and estimate the proportion of individual genetic admixture; however, the utility of these markers remains questionable.     

New insights into the genetic instability of streptomyces

Abstract The high level of genetic instability in Streptomyces ambofaciens is related to large scale DNA rearrangements (deletions and DNA amplifications) which occur within a 2 Mb chromosomal region. The genome of several Streptomyces species is linear and the unstable region is present at the chromosomal extremities. This has raised the questions of the role of the unstable region (which is dispensable under laboratory conditions), the functions of the genes present in this area, and the relationships between instability and chromosomal linearity. The unstable region of Streptomyces and the replication termini of several other microorganisms, including Escherichia coli , share numerous common traits. This suggests that the unstable region of Streptomyces includes the replication terminus, and that chromosomal instability is related to the termination process.     

Estimating heritable genetic contributions to innate immune and endocrine phenotypic correlations: A need to explore repeatability

The immune system plays an important role in enhancing an individual's ability to survive in a world inhabited by pathogens and parasites. The innate immune system is regulated by processes encoded in an individual's genome, providing an avenue for selection to act on this system, as well as the phenotypic relationships generated between this system and other traits of interest. While relationships between innate immunity and endocrine traits (e.g. testosterone) have been reported often in the literature, these relationships are complex and may differ under varying environmental conditions. To better understand the relative contribution of innate immunity (or an endocrine or behavioral trait) to a phenotypic correlation with another trait, an estimation of the underlying heritable genetic variation of the trait of interest is needed. An upper level estimate of the heritability of such traits can be obtained from calculating its repeatability. We conducted a literature review to determine how often repeated samples of measures of innate immune function were conducted and repeatability estimates obtained. This review revealed a very limited number of repeatability estimates, with a large range (0.0–0.9); estimates were exclusively from livestock that have undergone strong artificial selection. This observation of the present literature suggests more work is needed in non-domesticated and free-living animals to begin to understand the underlying genetic contribution of innate immune function to phenotypic correlations of interest (e.g. testosterone and immunity) to behavioral ecologists, evolutionary physiologists and ecoimmunologists.     

Impact of genetic insights into calpain biology

Calpain has long been an enigmatic enzyme, although it is involved in a variety of biological phenomena. Recent progress in calpain genetics has highlighted numerous physiological contexts in which the functions of calpain are of great significance. This review focuses on recent findings in the field of calpain genetics and the importance of calpain function. Calpain is an intracellular Ca(2+)-dependent cysteine protease (EC 3.4.22.17; Clan CA, family C02) found in almost all eukaryotes. It is also present in a few bacteria, but not in archaebacteria. Calpain has limited proteolytic activity; rather, it transforms or modulates the structure and/or activity of its substrates. It is, therefore, referred to as a 'modulator protease'. Within the human genome, 15 genes (CAPN1-3, CAPN5-16) encode a calpain-like protease (CysPc) domain along with several different functional domains. Thus, calpains can be regarded as a distinct family of versatile enzymes that fulfil numerous tasks in vivo. Genetic studies show that a variety of defects in many different organisms, including lethality, muscular dystrophies and gastropathy, actually stem from calpain deficiencies. The cause-effect relationships identified by these studies form the basis for ongoing and future studies regarding the physiological role of calpains.     

New insights into the genetic diversity of zooxanthellae in Mediterranean anthozoans

Symbiotic dinoflagellates of the genus Symbiodinium, also called zooxanthellae, are found in association with a wide diversity of shallow-water anthozoans. The Symbiodinium genus includes numerous lineages, also referred to as clades or phylotypes, as well as a wide diversity of genetic sub-clades and sub-phylotypes. There are few studies characterizing the genetic diversity of zooxanthellae in Mediterranean anthozoans. In this study, we included anthozoans from the Western Mediterranean Sea and by means of internal transcriber (ITS) and large sub-unit (LSU) rRNA markers we corroborate what has been previously identified, demonstrating that phylotype “Temperate A” is very common among host Cnidaria in this basin. Our finding of fixed differences in ITS and LSU markers that correspond to different host taxa, indicate that this clade may comprise several closely-related species. Previous studies have reported the occurrence of Symbiodinium psygmophilum (formerly sub-clade B2) associated with Oculina patagonica and Cladocora caespitosa in the Eastern Mediterranean. Here, we identify this association in O. patagonica from the Western Mediterranean but not in C. caespitosa, suggesting some differences in symbiotic combinations between the Western and Eastern Mediterranean Basins.     

Y-chromosomal insights into the genetic impact of the caste system in India

The caste system has persisted in Indian Hindu society for around 3,500 years. Like the Y chromosome, caste is defined at birth, and males cannot change their caste. In order to investigate the genetic consequences of this system, we have analysed male-lineage variation in a sample of 227 Indian men of known caste, 141 from the Jaunpur district of Uttar Pradesh and 86 from the rest of India. We typed 131 Y-chromosomal binary markers and 16 microsatellites. We find striking evidence for male substructure: in particular, Brahmins and Kshatriyas (but not other castes) from Jaunpur each show low diversity and the predominance of a single distinct cluster of haplotypes. These findings confirm the genetic isolation and drift within the Jaunpur upper castes, which are likely to result from founder effects and social factors. In the other castes, there may be either larger effective population sizes, or less strict isolation, or both. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. Tatiana Zerjal and Arpita Pandya contributed equally to this work.     

Novel insights into the genetic background of genetically modified mice

Unclear or misclassified genetic background of laboratory rodents or a lack of strain awareness causes a number of difficulties in performing or reproducing scientific experiments. Until now, genetic differentiation between strains and substrains of inbred mice has been a challenge. We have developed a screening method for analyzing inbred strains regarding their genetic background. It is based on 240 highly informative short tandem repeat (STR) markers covering the 19 autosomes as well as X and Y chromosomes. Combination of analysis results for presence of known C57BL/6 substrain-specific mutations together with autosomal STR markers and the Y-chromosomal STR-haplotype provides a comprehensive snapshot of the genetic background of mice. In this study, the genetic background of 72 mouse lines obtained from 18 scientific institutions in Germany and Austria was determined. By analyzing only 3 individuals per genetically modified line it was possible to detect mixed genetic backgrounds frequently. In several lines presence of a mispairing Y chromosome was detected. At least every second genetically modified line displayed a mixed genetic background which could lead to unexpected and non-reproducible results, irrespective of the investigated gene of interest.     

New insights into the genetic regulation of homologue disjunction in mammalian oocytes

Mammalian oocytes execute a unique meiotic programme involving 2 arrest stages and an unusually protracted preamble to chromosome segregation during the first meiotic division (meiosis I). How mammalian oocytes successfully navigate their exceptional meiotic journey has long been a question of immense interest. Understanding the minutiae of female mammalian meiosis I is not merely of academic interest as 80-90% of human aneuploidy is the consequence of errors arising at this particular stage of oocyte maturation, a stage with a peculiar vulnerability to aging. Recent evidence indicates that oocytes employ many of the same cast of proteins during meiosis I as somatic cells do during mitosis, often to execute similar tasks, but intriguingly, occasionally delegate them to unexpected and unprecedented roles. This is epitomised by the master cell-cycle regulon, the anaphase-promoting complex or cyclosome (APC/C), acting in concert with a critical APC/C-targeted surveillance mechanism, the spindle assembly checkpoint (SAC). Together, the APC/C and the SAC are among the most influential entities overseeing the fidelity of cell-cycle progression and the precision of chromosome segregation. Here I review the current status of pivotal elements underpinning homologue disjunction in mammalian oocytes including spindle assembly, critical biochemical anaphase-initiating events, APC/C activity and SAC signalling along with contemporary findings relevant to progressive oocyte SAC dysfunction as a model for age-related human aneuploidy.     

The application of non-invasive genetic tagging reveals new insights into the clay lick use by macaws in the Peruvian Amazon

Genetic tagging, the unique identification of individuals by their DNA profile, has proven to be an effective method for research on several animal species. In this study we apply non-invasive genetic tagging from feather samples to reveal the genetic structure and estimate local population size of red-and-green macaws (Ara chloropterus) without the need to capture these animals. The study was centered in the Tambopata region of the Peruvian Amazon. Here macaws frequently visit clay licks and their naturally molted feathers provide a unique source of non-invasively sampled DNA. We analyzed 249 feathers using nine microsatellite loci and identified 221 unique genotypes. The remainder revealed 21 individuals which were ‘recaptured’ one or more times. Using a capture-mark-recapture model the average number of different individuals visiting clay licks within one breeding season was estimated to fall between 84 and 316 individuals per clay lick. Analysis of population genetic structure revealed only small genetic differences among regions and clay licks, suggesting a single red-and-green macaw genetic population. Our study confirms the utility of non-invasive genetic tagging in harsh tropical environment to obtain crucial population parameters about an abundant parrot species that is very difficult to capture in the wild.     

Admixture mapping: from paradigms of race and ethnicity to population history

Admixture mapping is a whole genome association strategy that takes advantage of population history-or genetic ancestry-to map genes for complex diseases. However, because it uses racial/ethnic groupings to examine differential disease risk, admixture mapping raises ethical and social concerns. While there has been much theoretical commentary regarding the ethical and social implications of population-based genetic research, empirical data from stakeholders most closely involved with these studies is limited. One of the first admixture mapping studies carried out was a scan for Multiple Sclerosis (MS) risk factors in an African-American population. Applying qualitative research methods, we used this example to explore developing views, experiences and perceptions of the ethical and social implications of admixture mapping and other population-based research-their value, risks and benefits, and the future prospects of the field. Additionally, we sought to understand how social and ethical risks might be mitigated, and the benefits of this research optimized. We draw on in-depth, one-on-one interviews with leading population geneticists, genome scientists, bioethicists, and African-Americans with MS. Here we present our findings from this unique group of key informants and stakeholders.     

Probiogenomics as a tool to obtain genetic insights into adaptation of probiotic bacteria to the human gut

Bifidobacteria and lactobacilli are widely exploited as health-promoting bacteria in many functional foods. However, the molecular mechanisms as to how these bacteria positively impact on host health are far from completely understood. For this reason these microorganisms represent a growing area of interest with respect to their genomics, molecular biology and genetics. Recent genome sequencing of a large number of strains of bifidobacteria and lactobacilli has allowed access to the complete genetic makeup of representative members of these bacteria. Here, we will discuss how the analysis of genomic data has helped us to understand the mechanisms by which these bacteria adapt to the specific environment of the gastrointestinal tract, while also revealing genetic functions that mediate specific host-microbe interactions.     

Hyaluronan: genetic insights into the complex biology of a simple polysaccharide

It is appropriate that this review should appear in a volume dedicated to Mert Bernfield. Much of my interest in the cell biology of the extracellular matrix, particularly during development, echoes Mert's pioneering studies. His kind but provocative questioning during meetings is especially missed. The glycosaminoglycan hyaluronan is ubiquitous, and is especially abundant during embryogenesis. Hydrated matrices rich in hyaluronan expand the extracellular space, facilitating cell migration. The viscoelastic properties of hyaluronan are also essential for proper function of cartilage and joints. Recent understanding of hyaluronan biology has benefited from the identification of genes encoding hyaluronan synthases and hyaluronidases, genetic analysis of the roles of hyaluronan during development, elucidation of the biochemical mechanisms of hyaluronan synthesis, and by studies of human genetics and tumors. This review focuses on recent studies utilizing hyaluronan-deficient, gene targeted mice with null alleles for the principal source of hyaluronan during mid-gestation, hyaluronan synthase-2 (has-2). Published in 2003.     

Quantitative genetic insights into the coevolutionary dynamics of male and female genitalia

The spectacular variability that typically characterizes male genital traits has largely been attributed to the role of sexual selection. Among the evolutionary mechanisms proposed to account for this diversity, two processes in particular have generated considerable interest. On the one hand, females may exploit postcopulatory mechanisms of selection to favour males with preferred genital traits (cryptic female choice; CFC), while on the other hand females may evolve structures or behaviours that mitigate the direct costs imposed by male genitalia (sexual conflict; SC). A critical but rarely explored assumption underlying both processes is that male and female reproductive traits coevolve, either via the classic Fisherian model of preference-trait coevolution (CFC) or through sexually antagonistic selection (SC). Here, we provide evidence for this prediction in the guppy (Poecilia reticulata), a polyandrous livebearing fish in which males transfer sperm internally to females via consensual and forced matings. Our results from a paternal half-sibling breeding design reveal substantial levels of additive genetic variation underlying male genital size and morphology—two traits known to predict mating success during non-consensual matings. Our subsequent finding that physically interacting female genital traits exhibit corresponding levels of genetic (co)variation reveals the potential intersexual coevolutionary dynamics of male and female genitalia, thereby fulfilling a fundamental assumption underlying CFC and SC theory.