Genetics today : proceedings of the XI International Congress of Genetics, The Hague, The Netherlands, September 1963 / edited by S. J. Geerts.

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Detecting immigration by using multilocus genotypes

Immigration is an important force shaping the social structure, evolution, and genetics of populations. A statistical method is presented that uses multilocus genotypes to identify individuals who are immigrants, or have recent immigrant ancestry. The method is appropriate for use with allozymes, microsatellites, or restriction fragment length polymorphisms (RFLPs) and assumes linkage equilibrium among loci. Potential applications include studies of dispersal among natural populations of animals and plants, human evolutionary studies, and typing zoo animals of unknown origin (for use in captive breeding programs). The method is illustrated by analyzing RFLP genotypes in samples of humans from Australian, Japanese, New Guinean, and Senegalese populations. The test has power to detect immigrant ancestors, for these data, up to two generations in the past even though the overall differentiation of allele frequencies among populations is low.

The genetics of caloric restriction in Caenorhabditis elegans

Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans. To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode Caenorhabditis elegans. Mutations in many genes (eat genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most eat mutations significantly lengthen life span (by up to 50%). In C. elegans, mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation (age-1, daf-2, daf-16, and daf-28) and a mechanism involving genes that affect the rate of development and behavior (clk-1, clk-2, clk-3, and gro-1). We find that the long life of eat-2 mutants does not require the activity of DAF-16 and that eat-2; daf-2 double mutants live even longer than extremely long-lived daf-2 mutants. These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants. In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes.

Ethnohistory, genetics, and cancer mortality in Europeans

Geographic variation in cancer rates is thought to be the result of two major factors: environmental agents varying spatially and the attributes, genetic or cultural, of the populations inhabiting the areas studied. These attributes in turn result from the history of the populations in question. We had previously constructed an ethnohistorical database for Europe since 2200 B.C., permitting estimates of the ethnic composition of modern European populations. We were able to show that these estimates correlate with genetic distances. In this study, we wanted to see whether they also correlate with cancer rates. We employed two data sets of cancer mortalities from 42 types of cancer for the European Economic Community and for Central Europe. We subjected spatial differences in cancer mortalities, genetic, ethnohistorical, and geographic distances to matrix permutation tests to determine the magnitude and significance of their association. Our findings are that distances in cancer mortalities are correlated more with ethnohistorical distances than with genetic distances. Possibly the cancer rates may be affected by loci other than the genetic systems available to us, and/or by cultural factors mediated by the ethnohistorical differences. We find it remarkable that patterns of frequently ancient ethnic admixture are still reflected in modern cancer mortalities. Partial correlations with geography suggest that local environmental factors affect the mortalities as well.

Population genetics of Ice Age brown bears

The Pleistocene was a dynamic period for Holarctic mammal species, complicated by episodes of glaciation, local extinctions, and intercontinental migration. The genetic consequences of these events are difficult to resolve from the study of present-day populations. To provide a direct view of population genetics in the late Pleistocene, we measured mitochondrial DNA sequence variation in seven permafrost-preserved brown bear (Ursus arctos) specimens, dated from 14,000 to 42,000 years ago. Approximately 36,000 years ago, the Beringian brown bear population had a higher genetic diversity than any extant North American population, but by 15,000 years ago genetic diversity appears similar to the modern day. The older, genetically diverse, Beringian population contained sequences from three clades now restricted to local regions within North America, indicating that current phylogeographic patterns may provide misleading data for evolutionary studies and conservation management. The late Pleistocene phylogeographic data also indicate possible colonization routes to areas south of the Cordilleran ice sheet.

Microsatellites provide evidence for Y chromosome diversity among the founders of the New World

Recently, Y chromosome markers have begun to be used to study Native American origins. Available data have been interpreted as indicating that the colonizers of the New World carried a single founder haplotype. However, these early studies have been based on a few, mostly complex polymorphisms of insufficient resolution to determine whether observed diversity stems from admixture or diversity among the colonizers. Because the interpretation of Y chromosomal variation in the New World depends on founding diversity, it is important to develop marker systems with finer resolution. Here we evaluate the hypothesis of a single-founder Y haplotype for Amerinds by using 11 Y-specific markers in five Colombian Amerind populations. Two of these markers (DYS271, DYS287) are reliable indicators of admixture and detected three non-Amerind chromosomes in our sample. Two other markers (DYS199, M19) are single-nucleotide polymorphisms mostly restricted to Native Americans. The relatedness of chromosomes defined by these two markers was evaluated by constructing haplotypes with seven microsatellite loci (DYS388 to 394). The microsatellite backgrounds found on the two haplogroups defined by marker DYS199 demonstrate the existence of at least two Amerind founder haplotypes, one of them (carrying allele DYS199 T) largely restricted to Native Americans. The estimated age and distribution of these haplogroups places them among the founders of the New World.

A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG)

The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology.

Atlas of Genetics and Cytogenetics in Oncology and Haematology, updated

The ‘Atlas of Genetics and Cytogenetics in Oncology and Haematology’ (http://www.infobiogen.fr/services/chromcancer) is an Internet database aimed at genes involved in cancer, cytogenetics and clinical entities in cancer, and cancer-prone diseases. It presents information in concise and updated reviews (cards) or longer texts (deep insights), a (new) case report section, a huge portal towards genetics and/or cancer databases, and teaching items in genetics for students in medicine and the sciences. This database is made for and by clinicians and researchers in the above-mentioned fields, who are encouraged to contribute. It deals with cancer research, genomics and cytogenomics. It is at the crossroads of research, post-university teaching and telemedicine. The Atlas is available at no cost.

Genetics and the population history of Europe

Analysis of genetic variation among modern individuals is providing insight into prehistoric events. Comparisons of levels and patterns of genetic diversity with the predictions of models based on archeological evidence suggest that the spread of early farmers from the Levant was probably the main episode in the European population history, but that both older and more recent processes have left recognizable traces in the current gene pool.