正しい方法がわかる臨床基本手技 : from the New England journal of medicine

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, Mexico and Peru). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

/pdf/admixture-in-latin-america-geographic-structure-phenotypic-5etaz9nbwh.pdf

Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

This review explores the limitations of self-reported race, ethnicity, and genetic ancestry in biomedical research. Various terminologies are used to classify human differences in genomic research including race, ethnicity, and ancestry. Although race and ethnicity are related, race refers to a person’s physical appearance, such as skin color and eye color. Ethnicity, on the other hand, refers to communality in cultural heritage, language, social practice, traditions, and geopolitical factors. Genetic ancestry inferred using ancestry informative markers (AIMs) is based on genetic/genomic data. Phenotype-based race/ethnicity information and data computed using AIMs often disagree. For example, self-reporting African Americans can have drastically different levels of African or European ancestry. Genetic analysis of individual ancestry shows that some self-identified African Americans have up to 99% of European ancestry, whereas some self-identified European Americans have substantial admixture from African ancestry. Similarly, African ancestry in the Latino population varies between 3% in Mexican Americans to 16% in Puerto Ricans. The implication of this is that, in African American or Latino populations, self-reported ancestry may not be as accurate as direct assessment of individual genomic information in predicting treatment outcomes. To better understand human genetic variation in the context of health disparities, we suggest using “ancestry” (or biogeographical ancestry) to describe actual genetic variation, “race” to describe health disparity in societies characterized by racial categories, and “ethnicity” to describe traditions, lifestyle, diet, and values. We also suggest using ancestry informative markers for precise characterization of individuals’ biological ancestry. Understanding the sources of human genetic variation and the causes of health disparities could lead to interventions that would improve the health of all individuals.

/pdf/self-reported-race-ethnicity-in-the-age-of-genomic-research-5c52di3tf2.pdf

Self-reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities

Do we need another review series now we have Nature Review Genetics, Trends in Genetics, and all the current opinion journals? Does anybody have time to read them now? Must we have another high impact journal almost every month? The answer depends as much on the reader's taste as on the way the dish is served. In this regard the annual reviews series has always been unique because of its consistent high quality and broad scope. The editors of the new Annual Review of Genomics and Human Genetics aim to cover these fields in the broadest sense and this they do. This means that while few will read this book from cover to cover, there certainly is something to savour here for everybody. In this first issue for instance, there is a fascinating account by James Crow of his personal experience with human genetics as it developed from its early beginnings with the chromosome maps of the Sturtevant and Morgan labs working on Drosophila. Crow takes us back in time so that we can experience what great skills and determination it took to make those early important discoveries. It is enlightening to see cytogenetics described as `pitiful' in the first half of the last century. But what joy it is to read about discoveries that might have been made but weren't. As Crow says: `some were overlooked, others were simply regarded as uninteresting'. There is a lesson here for all of us. Surely there must be things out there even now to discover which are not recognized because we cannot see beyond our own fixed beliefs? There is much more in this 580-page first volume. Many chapters will appeal to clinical geneticists and those working in diagnostic settings. Scholarly accounts of the genetics of trinucleotide repeat diseases, disorders of iron metabolism, Williams syndrome, newborn screening, and public concern about genetics, are examples of this. On the other hand, fundamental aspects of genetics and genomics are included also, such as estimating allele age, gene family evolution, methods for large scale analysis of sequence variation, or bioinformatic tools. Clearly, this new genomics and human genetics volume is much more appealing to human geneticists than the annual review of genetics which has been on the shelves of many human genetics department's libraries. In short: there is something here for everybody. This new series of high quality reviews can compete with the best in the field.

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Annual Review of Genomics and Human Genetics

Many panels of ancestry informative single nucleotide polymorphisms have been proposed in recent years for various purposes including detecting stratification in biomedical studies and determining an individual's ancestry in a forensic context. All of the panels have limitations in their generality and efficiency for routine forensic work. Some panels have used only a few populations to validate them. Some panels are based on very large numbers of SNPs thereby limiting the ability of others to test different populations. We have been working toward an efficient and globally useful panel of ancestry informative markers that is comprised of a small number of highly informative SNPs. We have developed a panel of 55 SNPs analyzed on 73 populations from around the world. We present the details of the panel and discuss its strengths and limitations.

Progress toward an efficient panel of SNPs for ancestry inference

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2>0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.

/pdf/development-of-a-panel-of-genome-wide-ancestry-informative-2uc33qjeih.pdf

Patricia Taboada

Papers

Development of a Panel of Genome-Wide Ancestry Informative Markers to Study Admixture Throughout the Americas