Genetic admixture studies on four in situ evolved, two migrant and twenty-one ethnic populations of Tamil Nadu, south India.

We analysed the genetic structure of ≈ 1000 samples representing 27 ethnic groups settled in Tamil Nadu, south India, derived from two linguistic families (Dravidians and Indo-Europeans) representing four religious groups (Hinduism, Islam, Christianity and Jainism) using 11 mtDNA markers. Out of 27 ethnic groups, four are in situ populations (Anglo-Indian, Labbai Muslim, Nadar Christian and south Indian Jain) and two are migrants (Gypsy and north Indian Jain) from north India to Tamil Nadu, and 21 are native ethnic groups. Six of the markers we used were monomorphic (HaeIII663, HpaI3592, AluI5176, AluI7025, AluI13262, 9-bp deletion) and five markers were polymorphic (DdeI10394, AluI10397, HinfI12308, HincII13259 and HaeIII16517). Haplogroup frequencies, genetic affinities and admixture analysis are based on the genotype data of polymorphic markers observed in these populations. Haplogroup frequencies indicate that various ethnic groups entered Tamil Nadu during different time periods. Genetic affinities and admixture estimates revealed that the ethnic groups possessing advanced knowledge of farming cluster in a branch (C), and could be the late arrived settlers as agriculture, was introduced to this region at about 5 to 3 thousand years ago. In situ ethnic groups appear to have arisen at various times as a result of the prevailing dominant socio-cultural forces. Hierarchical Hindu caste system created many ethnic groups in the history of its existence; some of them became isolated for considerable period of time. Over all, among Tamil ethnic groups, in spite of caste systems' rigidity, built in flexibility in the system in the form of hypergamy and hypogamy had allowed maternal gene flow between them.

Autosomal recessive retinitis pigmentosa locus RP28 maps between D2S1337 and D2S286 on chromosome 2p11-p15 in an Indian family.

Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous disorders characterised by night blindness, constriction of visual field, and dystrophic changes of the retina. Previous genetic studies have shown extensive allelic and non-allelic genetic heterogeneity of RP. Here we describe an Indian family with multiple consanguineous marriages and a total of four patients with autosomal recessive (AR) RP. The homozygosity mapping strategy was successfully used and indicated close linkage between the disease locus and D2S380, D2S441, D2S291, and D2S1394 with maximum lod scores between 1.51-3.07 at theta=0.00. The analysis of multiply informative meioses maps the locus (RP28) for ARRP in this family between D1S1337 and D2S286 on 2p11-p15. The involvement of visinin (VSNL1), a promising candidate gene assigned to chromosome 2p by previous studies, has been excluded by the absence of linkage.

[Annual school and menarche rhythms (vacation-study)]. / Ritmos anuales escolar (vacaciones-estudio) y de menarquia.

BACKGROUND: It has been hypothesized that the yearly menarche rhythm could be caused by the seasonal variation of photoperiod and temperature or by the annual distribution of the scholar vacation and study periods. AIM: To test the hypothesis that the distribution of study vacation periods is a condition that modifies the annual menarche rhythm. SUBJECTS AND METHODS: Two thousand ninety four school girls from Chile, 2,356 girls from Madras, India, 3,454 girls from Medellin, Colombia and 2,627 girls from Debrecen, Hungary, were studied. They were asked about the month of their menarche. Vacation months were considered those with more than 6 days of leave from school. RESULTS: The seasonal hypothesis was refuted because there were contradictions with the expected antithetical behavior in both hemispheres, there was a significant heterogeneity of the yearly menarche among girls from the same region, the expected cline of the menarche frequency variance from equator to poles was not observed, finding an antithetical cline instead and there was a significant heterogeneity among months of the same season. On the other hand, months with vacation periods coincided significantly with peaks of menarche, while study months had lower proportion of menarche (total binomial probability < 10(-6)). Girls whose month of menarche was the same as their month of birth, did not agree completely with the vacation-study hypothesis as the rest of the sample. CONCLUSIONS: Vacation periods influenced menarche rhythm. However, these periods coincide with most cultural events and this strong association needs further study to be considered causal. It is not possible to assume school stress as the main explanatory variable. Ontogenetic factors such as birth imprinting also can influence the menarche rhythm, as shown in girls whose month of menarche coincided with their month of birth.

Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa. Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA. Disease genes implicated in other forms of arCSRD are expected to encode proteins present in the neuroretina or in the retinal pigment epithelium (RPE). The RPE, a monolayer of cells separating the vascular-rich choroid and the neuroretina, is in intimate contact with the outer segments of rods and cones via the microvilli surrounding the photoreceptors. The RPE expresses a tissue-specific and evolutionarily highly conserved 61 kD protein (RPE65) present at high levels in vivo. Although the function of RPE65 is not yet known, an important role in the RPE/photoreceptor vitamin-A cycle is suggested by the fact that RPE65 associates both with serum retinol-binding protein and with the RPE-specific 11-cis retinol dehydrogenase, an enzyme active in the synthesis of the visual pigment chromophore 11-cis retinal. Here we report that the analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation (Pro363Thr), two point mutations affecting splicing (912 + 1G-->T and 65 + 5G-->A) and two small re-arrangements (ins144T and 831del8) on a total of nine alleles of five patients with arCSRD. In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina.

ABO segregation distortion in Visakhapatnam, India.

Distortions in mother-infant, mother-child and father-child segregation for the ABO system as well as in the sex of offspring are described in a sample from a maternity service and from families of Visakhapatnam, India. Some distortions follow the expected fetomaternal incompatibility depression, others the expected feto-maternal induction of tolerance, and some remain unexplained. A differential action of selective factors on male and female fetuses, infants and children was also found, but no hypothesis could be postulated to explain it. The mother-infant matrix was found to be different from the mother-child matrix probably due to the inclusion of the reproductive time only in the mother-infant matrix. Unexpectedly, father-child segregation distortions were also found.

The genetic composition of an endogamous Adi-Dravidar population of Tamil Nadu.

A total of 204 blood samples were collected from healthy, unrelated Adi-Dravidars of Chengalput District, Tamil, India. These samples were screened for ABO and RH blood groups using the respective antisera. CP and ALB serum protein electrophoretic phenotypes were assessed. The chi 2 analysis for Hardy-Weinberg equilibrium revealed that the population fits in panmictic equilibrium. The results were compared with the findings reported for other populations of Southern India.

Parallel cousin marriages in Madras, Tamil Nadu: new trends in Dravidian kinship.

The frequency distribution of various consanguineous marriages was studied in the city of Madras, Tamil Nadu, South India. Parallel first cousin marriages (PFC) were found to occur in appreciable frequencies in all caste groups of Hindus. While it has been generally believed that PFC marriages among Hindus are mere exceptions and are usually not tolerated, our data show that they can no longer be treated as exceptions. The high frequency (27 per cent) of PFC marriages in some Hindu communities necessitates in-depth studies to elucidate the forces at work which go against the very fundamentals of Dravidian kinship.

Segregation distortion in Rh polymorphism.

Segregation distortion for the Rh system is reported. Mother-infant pairs (1018 pairs) from maternity service divisions of government hospital and 216 complete families with a total of 692 children, of Visakhapatnam (Andhra Pradesh, South India) were typed for the D-d alleles of Rh system. The segregations analysis made by means of the T matrix method of ITO matrices, assuming Hardy-Weinberg equilibrium, reveals that: Rh-positive mothers produce fewer Rh-negative children with significance and Rh-negative mothers produce more Rh-positive children with less significance than expected in both the mother-child and family studies. This results in a reduction in the d allele from mothers to their children. Known Rh antigenic specificities and reproductive compensation do not explain the observed distortion. Other selectively acting forces probably linked to Rh compatibility system seem to be operating to gain d alleles to maintain Rh polymorphism.

Gene differentiation at the ABO locus in twenty castes and twenty-two tribes of Andhra Pradesh, India.

Using gene frequency data for the ABO locus so far available, gene differentiation and gene identity between 20 castes and 22 tribes of Andhra Pradesh were determined. The interpopulation gene diversity is 1.4 and 1.6% of total genic variation in castes and tribes, respectively. Difficulties in interpreting genetic diversity using just one genetic system is discussed.

Acuity of selective mechanisms operating on ABO, Rh, and MN blood groups.

Selection in ABO, Rh, and MN blood groups was studied in 216 matings and their children in an endogamous population. Incompatibility status with respect to these three systems was considered simultaneously. There is no effect of incompatibility on number of pregnancies. Analysis of variance between groups confirms that prenatal loss is associated with incompatibility, and it is greater when the matings are incompatible for any two systems. There is no significant intergenerational change in ABO and Rh polymorphisms. Segregation analysis for the ABO system suggests that there is no significant difference in the proportion of A, B, and O children, based on the compatibility of the parents, while analysis for Rh-D system showed a segregation distortion which is not related to the known antigenic specificities (mother-child incompatibility).

Proportion of low birth weight infants in Visakhapatnam (India) and its relationship with maternal age, parity and infants survival.

The percentage of low birth weight infants (LBWI) weighing less than 2270 g in Visakhapatnam (Andhra Pradesh) is relatively higher (12.8%) than in other parts of India. The frequency of LBWI is high at birth order 1 and 2. Thereafter the curve does not show any consistency although the mean per cent of LBWI is lesser than in birth order 1 and 2. The minimum frequency is at birth order 3. The maternal classes less than or equal to 20-29 years show a gradual decrease in the frequency of LBWI with increasing age. For mothers of greater than or equal to 30-39 years of age a general U-shaped relation is found. The overall distribution of neonatal deaths is bimodal, with a peak at less than 1350 g and at 1810 g.

PIP: 12.8% of 11,241 births occurring in the 2 major hospitals in Visakhapatnam, India, were classified as low birthweight (defined as less than 2270 grams). The frequency of low birthweight was highest at birth orders 1 and 2 and lowest at birth order 3. A gradual decrease in the frequency of low birthweight with increasing maternal age was noted in mothers age 29 years and younger. A general U-shaped association was found for mothers over this age. The overall distribution of neonatal deaths was bimodal, with a peak at less than 1350 grams and at 1810 grams. The percentage of low birthweight infants in this area of India is relatively higher than that in other areas. Low birthweight is believed to be a result of a complex of factors, including nutrition, placental size, maternal nutrition, maternal infection, drug use, preterm delivery, multiple pregnancy, chromosomal and congenital anomalies, and primary growth failure syndromes.

Gene differentiation in four subcastes of Brahmins from Visakhapatnam, Andhra Pradesh.

Blood group (ABO, MN, Rh, CcDEe) polymorphisms are reported here for 4 strictly endogamous subcastes of Andhra Brahmins. The coefficient of gene differentiation calculated from the gene frequencies is 0.87% demonstrating that only a small fraction of the total gene diversity is attributable to the differences between subcastes. In spite of the strict endogamy for the past 10-14 centuries, 99.13% of gene differentiation exists within the subcastes.

Fertility and mortality differences in relation to maternal body size.

The relationship between maternal stature, number of conceptions, offspring mortality and number of surviving children was studied in 291 Jalari women. Maternal stature averaged 150.98 cm, maternal age 35 years, number of conceptions 5.1 and number of surviving children 4.2. Adjusting for age and number of conceptions, the relationship between maternal stature and surviving children is significantly negative. Shorter women show significantly higher number of conceptions and surviving children than taller women (P less than 0.05). Intensity of natural selection (I) is computed for height and weight.

Variability of selection opportunities with changing socio-cultural environments.

Opportunity for selection has been studied against their contrasting socioeconomic and cultural backgrounds in two endogamous populations, namely, Brahmins and Jalaris of Visakhapatnam, India. Total selection was slightly higher among the better off Brahmins than in Jalaris. But a marked qualitative and quantitative variation was found in the contributing components; the fertility differential was circa 60% in Brahmins while the mortality differential was circa 60% in Jalaris according to the Crow Index. The decreased mortality differential in Brahmins suggests that this component was directly affected by the better socio-economic level and reflects on the population's transitional phase. Further, the If value fell to a half in women who completed their fertility by family planning when compared to women who completed their fertility by menopause, thus reducing the variance in fertility component in the family planning group.

Familial appraisal of colorblindness in school children of an Indian population.

A total 2000 unrelated school children were screened for colorblindness in Vishakhapatnam, India. Whether the protan and deutan defects are the result of mutations at one locus or at two loci has not been completely resolved, although the evidence favors two discrete loci. The investigation was extended to the families of the 40 color vision anomalous children to study the descendance patterns of these two loci. The importance of these observations are discussed.

Variability of genetic load with changing socio-cultural environment.

Variability in genetic load has been studied against their contrasting socioeconomic and cultural backgrounds in two endogamous populations, namely, the well-off Brahmins and the low income Jalaris of Visakhapatnam, India. The A (genetic and environmental damage) and B (hidden genetic damage) estimates are higher in Jalaris. Decreased A estimates indicate the better medical care in Brahmins; the value of B could be low since many of the deaths in consanguineous families due to infectious diseases are now rarer. The genetic load (B/A ratio) indicates that the average gamete carries 0.057 and 2.123 deleterious genes, respectively, in Brahmins and Jalaris, which, if made homozygous, would kill an individual before reproductive age. The load is 35 times higher in Jalaris; this may be due to their higher inbreeding level. Contrasting socioeconomic differences and meagre medical aid might add another bias towards relatively higher B/A in Jalaris. In general the observed genetic load in both populations are lower than in other studies which may be due to gradual elimination of deleterious genes by continued practice of inbreeding.