Ethnogenomic diversity of Caucasus, Daghestan.

Autosomal short-tandem repeats (STRs) were typed in ethnic populations of Kubachians, Dargins, Avars, Lezgins, Kumiks, and Nogais of the Caucasus (Daghestan, Russia) at the University of Utah. Daghestan ethnic populations demonstrated differences in STR allele frequency distributions, but these differences were much lower among these ethnic groups compared to worldwide ethnic groups. The observed genetic diversity was low while F(ST) values were high, both of which provided supporting evidence for small population sizes and high levels of isolation among the ethnic groups. An analysis of genetic distance from the three major continents, encompassing Daghestan populations and groups, reveals three distinct clusters: all populations of African affiliation, European and Daghestan populations except the Nogais, and Asian populations with ethnic Nogais.

The ascertainment of multiplex schizophrenia pedigrees from Daghestan genetic isolates (Northern Caucasus, Russia).

This article describes the preliminary ascertainment of multiplex schizophrenia pedigrees from the isolated mountain region of Daghestan (Northern Caucasus, Russia). Daghestan has a population of two million people and contains 26 aboriginal ethnic groups. Many of the ethnic groups reside in remote mountain villages that can be classified as 'primary isolates'. Prolonged reproductive isolation and severe environmental conditions in the highlands have created diverse, genetically isolated ethnic populations in Daghestan. A number of the isolates in this region contain large extended multiplex schizophrenia pedigrees that are ideal for genetic analyses. During summer expeditions of 1996 and 1997, 14 separate large multiplex schizophrenia pedigrees were ascertained from 14 different mountain villages. Of the 14 kindreds, one had 50 schizophrenic cases available for ascertainment, one had 32, and another had 24. Seven of the remaining pedigrees had between 11 and 23 living cases. Within the kindreds, the number of males with chronic schizophrenia was at least twice that of females. The average age of onset of schizophrenia is 21.2 years for offspring of consanguineous marriages and 17.4 years for offspring of nonconsanguineous marriages (P = 0.033). Although the pedigrees ascertained from the remote mountain villages may not be representative of the general population, they are unique kindreds for mapping schizophrenia susceptibility genes.

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy.

We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course. The second group included three patients with a slowly progressive distal myopathy first manifested in the late teens and confined to the tibial and calf muscles. Each of these two phenotypes segregated independently as an autosomal recessive trait, and muscle biopsies showed non-specific myopathic changes. Lastly, two male siblings exhibited an atypical variant of Duchenne muscular dystrophy confirmed by detection of a deletion in the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal recessive form of muscular dystrophy in this kindred, we performed molecular genetic studies on 67 family members and obtained significant evidence for linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of 5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for locus D2S291; multipoint linkage analysis confirmed the most likely location of a mutant gene near D2S291. The patients with LGMD and those with the distal muscular dystrophy phenotype share a common affected homozygous haplotype associated with the same founder chromosome; key recombinants defined D2S286 and D2S292 to be the closest loci flanking the mutant gene. Remarkably, two clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest that all three chromosome 2p-linked conditions may represent allelic disorders, i.e. different phenotypic expressions of a single gene.

Behavior genetic differences within and between defined human populations.

The small populations of the Caucasus offer a unique opportunity to consider concepts, such as heritability, which are often considered properties of a trait but which are really properties of a population. A comprehensive strategy is outlined for studying intra- and interpopulation genetic structure across a wide range of traits and environments. A three-way association is demonstrated between 12 of 16 psychophysiological traits, attitude, and the t allele for PTC sensitivity. Differences between populations and traits are evaluated in theoretical terms for morphological, physiological, and psychological measures. While decreases in performance with inbreeding are often predicted, in these small, isolated populations the effects are minimal.

Visual evoked potentials: phenotypic and genotypic variability.

Evoked potentials (EPs) provide a unique way of analyzing the relationship between genes and behavior. Individual differences in EPs, in response to light flashes of two intensities and pattern reversal, were studied in families from the isolated population Mechelta in the Northern Caucasus. While there were no age or sex differences in EP latency, or many age effects on amplitude, there were sex differences on the amplitude measures. Variation in the additive genetic determination of latency and amplitude measures is discussed. The largest estimates of additive genetic variation were found for the complexes of amplitude measures between the positive and negative waveforms.

Phenotypic and genetic affinities among ethnic populations in Daghestan (Caucasus, Russia): a comparison of polymorphic, physical, neurophysiological and psychological traits.

Daghestan contains many distinct populations characterized by different degrees of isolation, ethnic backgrounds and ecological conditions. This report introduces a large-scale family study conducted in seven Daghestan populations as well as in Moscow, using four categories of measures: (1) single gene polymorphisms, (2) anthropometric, (3) physiological, and (4) psychological quantitative traits. Such a study permits the analysis of both phenotypic and genetic variation within and between populations. The implications of such variation are discussed, especially in the context of the measures used. These derive from Soviet conceptualizations of the nervous system and related assessment of individual differences, and vary considerably from conventional Western approaches to behaviour. From the anthropometric through the physiological to the behavioural measures there was a clear trend towards increased phenotypic variation but reduced genetic variation. Possibly because the genetic variance was less on the more complex phenotypes, measures of generalized distance indicated much greater population similarity when based on phenotypic data on the genetic component of variation. Issues that arise when using behavioural traits to study human population diversity are discussed, particularly in relation to inbreeding and the specific cultural and linguistic practices in the Daghestan region.

Population-genetic analysis of some neurodynamic parameters of man.

Morphological, sensory and motor, and cognitive measures were obtained on 203 Moscow schoolchildren and 23 families (both parents and one child). There was evidence for assortative mating for all traits measured. Within groups (girls, boys, fathers, mothers), coefficients of variation (CV) were greatest for cognitive, intermediate for sensory and motor, and smallest for morphological measures. The authors theorize the CV reflects the degree of biological and social determination of a trait and thus also its heritability.