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Vitiligo is a depigmenting disorder of the skin caused by destruction of melanocytes. The depigmented skin has several abnormal functions, including some autonomic nervous functions. The inflammatory response in the depigmented skin is muted. Recent genetic and epidemiologic studies indicate that vitiligo affects men and women equally. The prevalence in the population is about one in 200. Vitiligo seems to be transmitted as a polygenic trait. New data suggest that it is not associated with autoimmune endocrine disorders, but more comprehensive studies are required.

Genetic polymorphisms for six blood groups, three red cell enzymes, three serum proteins, and hemoglobin were examined in sixteen central Indian tribal populations. Nine of the tribes belonged to Orissa, five to Madhya Pradesh, and two to Maharashtra. Eleven tribes spoke the Dravidian language, three Indo-Ayran, and two the language of the Austro-Asiatic families. The population structure of these tribal populations was analyzed at the inter- and intrastate and linguistic levels, using data for 13 genetic systems (38 alleles or haplotypes). Nine of the 13 loci showed significant heterogeneity in the 16 tribes, and the pattern of heterogeneity was also discernible in the different states and in the Dravidian-speaking tribes. As expected, the extent of genetic differentiation or gene diversity was the highest so far reported from central India. The mean FIS and HS for each locus in the different state, linguistic, and total tribal groups were consistently higher than the FST and GST values, respectively, showing that the genetic structure of each tribe is highly influenced by inbreeding. In a genetic affinity analysis by genetic distance the Indo-Aryan and Austro-Asiatic language groups showed little affinity with each other, although there was some tendency toward geographic affinity. The present analysis indicates that, in addition to genetic drift, gene flow, and selection, the genetic structure of the populations of central India is also highly influenced by sociocultural adaptation and inbreeding.

We have analyzed the CTG repeat length and the neighboring Alu insertion/deletion (+/-) polymorphism in DNA samples from 16 ethnically and geographically diverse human populations to understand the evolutionary dynamics of the myotonic dystrophy-associated CTG repeat. Our results show that the CTG repeat length is variable in human populations. Although the (CTG)5 repeat is the most common allele in the majority of populations, this allele is absent among Costa Ricans and New Guinea highlanders. We have detected a (CTG)4 repeat allele, the smallest CTG known allele, in an American Samoan individual. (CTG) > or = 19 alleles are the most frequent in Europeans followed by the populations of Asian origin and are absent or rare in Africans. To understand the evolution of CTG repeats, we have used haplotype data from the CTG repeat and Alu(+/-) locus. Our results are consistent with previous studies, which show that among individuals of Caucasian and Japanese origin, the association of the Alu(+) allele with CTG repeats of 5 and > or = 19 is complete, whereas the Alu(-) allele is associated with (CTG)11-16 repeats. However, these associations are not exclusive in non-Caucasian populations. Most significantly, we have detected the (CTG)5 repeat allele on an Alu(-) background in several populations including Native Africans. As no (CTG)5 repeat allele on an Alu(-) background was observed thus far, it was proposed that the Alu(-) allele arose on a (CTG)11-13 background. Our data now suggest that the most parsimonious evolutionary model is (1) (CTG)5-Alu(+) is the ancestral haplotype; (2) (CTG)5-Alu(-) arose from a (CTG)5-Alu(+) chromosome later in evolution; and (3) expansion of CTG alleles occurred from (CTG)5 alleles on both Alu(+) and Alu(-) backgrounds.

A genetic epidemiological study of serum lipid and lipoprotein levels was conducted among families of Marwaris residents in Calcutta. A total of 210 families, comprising over 100 individuals, were studied. Analyses were performed to estimate the genetic and environmental effects on the determination of high density lipoprotein cholesterol (HDL-C) and serum triglycerides (TG). Familial correlations for HDL-C and TG were estimated: parent-child and sib-sib correlations were found to be significant. Spouse correlations were not significant. Correlations between environments of siblings were significant. Genetic analysis of data on HDL-C and TG performed under a path model, taking genetic transmission and possible environmental associations among family members into account, indicated that lipid and lipoprotein levels adjusted and standardized for age, gender, education, occupation and disease status are primarily determined by genetic factors. The effects of environmental factors were also significant, although in comparison with genetic factors these effects were much smaller. The estimated genetic heritability for HDL-C was approximately 80 per cent, while that for TG was approximately 55 per cent. The genetic effects and environmental effects were not significantly different between adults and children.

We evaluate the blood pressure profile in relation to selected biological, behavioral, and socioeconomic factors among the Lepchas, a tribal population of Asian origin inhabiting the Dzongu area of northern Sikkim. The results show that mean systolic and diastolic blood pressures of Lepcha adults (aged 19 years and older), engaged primarily in agricultural practices, are conspicuously high and that the prevalence of essential hypertension (defined in terms of WHO criteria) is remarkably high as well, irrespective of sex. Significant effects of age on blood pressure were found. None of the anthropometric variables considered was a significant correlate of blood pressure in males, whereas triceps skinfold thickness was the only significant correlate of blood pressure in females. Systolic blood pressure among males was significantly affected by alcohol intake. Mean systolic and diastolic blood pressures consistently increase with increasing intake of alcohol in both sexes.

A genetic epidemiological study of blood pressure was conducted in two contrasting populations: the Marwaris of Calcutta and the Hindu middle-caste agriculturists of Digha. The Marwaris are heavier and significantly more obese than the agriculturists. The prevalence of hypertension among the Marwaris (17%) is more than tenfold higher than that among the agriculturists (1.4%). Genetic analysis of blood pressure data using a path model indicates that blood pressure levels (adjusted and standardized for age, gender, education level, and disease status) are primarily determined by environmental factors, as measured by their effects on anthropometric characters. The observed familial resemblance of blood pressure levels in the two populations is primarily due to cultural rather than genetic inheritance. Genetic and familial effects on covariation between anthropometric measures of obesity and blood pressure levels are perhaps so strong that there is no residual genetic heritability of adjusted blood pressure levels.

Spatial autocorrelation analysis performed on published data pertaining to caste and tribal populations of the Indian subcontinent has revealed that the surfaces of A, B and O allele frequencies are highly fractured. The only significant spatial autocorrelation was observed in respect of the A allele frequency among caste populations.

In DNA fingerprinting work, it is well known that, although fragment lengths of a sample are uncorrelated, measurement errors of fragment lengths are correlated. Unless the fragment length is very large, the measurement errors are directly proportional to fragment lengths. In the currently practiced matching procedures for forensic identification, these facts are ignored or inadequately used. Some of these issues are addressed in this study. Based on available empirical observations, an appropriate statistical model and techniques are proposed. These techniques lead to the definition and construction of elliptical match windows, instead of independent interval (linear) windows currently used. Simulation experiments indicate that the performance of the proposed procedure is superior to the current procedures. Further, the proposed procedure does not make use of some assumptions underlying the current procedures. Extensions of the procedure to utilize replicate measurements of crime-scene and/or suspect's samples are indicated.

In order to better understand the transgeneration liability for a substance abuse disorder, we investigated the impact of parental and familial substance abuse disorders on prepubertal boys. Specifically, the influence of each parent's substance abuse history and the effects of significant family aggregation of substance abuse disorders were tested as predictors of the child's behavioral disposition, IQ, and school achievement scores, while controlling for socioeconomic status (SES). Sons of substance abusing fathers were found to have higher externalizing and internalizing problem-behavior scores, lower IQ scores, and lower school achievement scores. Internalizing and externalizing problem-behavior scores were most strongly associated with bilineal parental substance abuse, whereas SES and paternal substance abuse were most strongly associated with IQ and school performance scores. The results are compatible with the hypothesis that although paternal substance abuse has an adverse impact on the son's functioning, bilineal parental substance abuse is associated with the greatest behavioral deviancy among prepubertal males and is associated with a greater liability for substance abuse.

Vitiligo is a dermatological disorder characterized by hypopigmentary patches that tend to become progressive over time. There are reports of extensive familial aggregation. A genetic model for this disorder was earlier proposed by us. This model postulates that recessive alleles at multiple unlinked autosomal loci interact epistatically in the pathogenesis of vitiligo. The present family study was primarily undertaken to cross-validate the proposed genetic model. Data on 194 families from the United States were collected. Each family was ascertained through an affected proband. Analyses of these data reveal that approximately 20% of probands have at least one first-degree relative afflicted with vitiligo. All types of first-degree relatives of probands show a significant risk of developing vitiligo. Results of segregation and robustness analyses reveal that the genetic model postulated by us previously is the most parsimonious model for the present family data set.

A total of 946 adults belonging to ten population groups of Uttar Pradesh and West Bengal were screened for HTLV-I using a gelatin particle agglutination test. The percentage of seroreactive cases varied from 0 to 5.8 per cent. The overall prevalence of seroreactivity was 2 per cent. Of the 19 seroreactive cases, 15 were subjected to Western blot analysis, none could be confirmed. HTLV-I infection is, therefore, absent in these populations.

Familial transmission plays an etiologically important role in psychoactive substance use disorders (PSUD). The delineation of the risk status of families is central to implementation of the "high risk paradigm" in studying liability characteristics for PSUD. We have utilized a latent variable approach to characterizing familial resemblance for PSUD which incorporates elements of both the affected parent design, as well as a genetic epidemiologic indicator of familial aggregation of disease. Family resemblance scores were computed for 175 families in which fathers either met diagnostic criteria for PSUD or did not. We then compared the problem behavior profiles of 10-12 year-old boys grouped by familial resemblance for PSUD, and by paternal PSUD only. Boys grouped by paternal PSUD only had higher problem behavior scores than controls across all scales except for somatic complaints. Boys from families that have significant PSUD familial resemblance were characterized by higher scores on measures of externalizing conduct and socialization problems. Thus, the familial resemblance approach was more specific for the externalizing problem behaviors that have been described in longitudinal studies of childhood risk factors for later substance abuse.

This population based study was conducted among the Marwaris of Calcutta, India. A total of 1,096 individuals from 151 randomly selected families were studied. Mean blood pressures were high. About 17% of the population was hypertensive, i.e., systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 95 mm Hg. The mean value of the ratio of total cholesterol to HDL cholesterol was 4.75. Comparison with a rural agricultural population showed that unadjusted blood pressure profiles differed significantly, but not when the profiles were adjusted for variation in concomitants (e.g., age, weight, fatness, etc.). It is hypothesized that the "intrinsic" blood pressure profiles of both populations are similar and that genes influencing physical variables (e.g., fatness) do not directly influence blood pressure. © 1994 Wiley-Liss, Inc., (Copyright © 1994 Wiley-Liss, Inc., A Wiley Company.)

The primary objective of the present study was to assess the impact of out-of-home employment on anxiety levels of mothers. A study group of working mothers resident in Calcutta (India) was compared with a socioeconomically similar group of non-working mothers with respect to their anxiety level, measured by the Anxiety Scale Questionnaire, in terms of the total anxiety score and its various personality components. The possible relationships between anxiety score and age of these mothers as well as their children were studied. Non-working mothers showed higher anxiety levels than their working counterparts with respect to the total anxiety score as well as its components, although the differences were statistically non-significant. The anxiety scores of non-working mothers showed increasing values with increasing age of children. This trend was absent among the working mothers. The age of these mothers was not related to their anxiety level.

Background and Design: Vitiligo is a disorder whose cause is not well understood. This study was undertaken to clarify whether genetic factors are involved in the pathogenesis of vitiligo. Data on 160 white kindreds living in the United States have been collected. Each family was ascertained through a proband afflicted with vitiligo. The nature and extent of familial aggregation and other relevant epidemiologic features have been determined., Results: The mean age at onset of vitiligo is about 19 years in male and about 24 years in female individuals. The percentage of probands reporting one or more first-degree relatives also afflicted with vitiligo is 20%. Children of probands are found to be afflicted about 1.7 times more commonly than other first-degree relatives. The relative risk (RR) for vitiligo is about 7 for parents, about 12 for siblings, and about 36 for children. For second-degree relatives, the RR varies between 1 and 16. Relative risks for all first- and second-degree relatives, except uncles and grandsons, are significant at the 5% level. In families in which one or more relatives of the proband are afflicted with vitiligo, the intrafamilial correlation of ages at onset of vitiligo is moderate (0.6). No statistically significant effect (at the 5% level) of parental age at first childbirth was seen on the proportion of offspring afflicted with vitiligo. No significant association of some commonly related diseases (eg, thyroid disorder or alopecia areata) was observed with vitiligo or with a family history of vitiligo., Conclusions: The extent of familial aggregation of vitiligo is statistically significant. The pattern of relationship between RR and degree of kinship indicates involvement of genetic factors, although it is not consistent with single-locus mendelian transmission.

On the basis of Rh blood group data on mother-child pairs collected from the maternity clinic of a hospital in Chile, Valenzuela and Harb postulated that there is a significant segregation distortion at the Rh locus. For data collected from a hospital, biases of ascertainment cannot be ruled out. For the Rh blood group locus, there is a strong possibility of preferential admission of Rh(-) pregnant women, especially of those Rh(-) women with Rh(+) husbands. We show that the evidence of segregation distortion vanishes when the possibility of such preferential admissions are taken into account.

Data pertaining to abdominal aortic aneurysm among first-degree relatives of 91 patients with abdominal aortic aneurysm are presented. The percentage of families with at least one affected first-degree relative of the proband (multiplex families) was 15.4%. In 21.4% of multiplex families parent-offspring transmission of abdominal aortic aneurysm was noted; in the remaining families only siblings were affected. The mean age at onset among probands was 67.3 years; that among all affected was 67.4 years. No statistically significant difference in the mean ages at onset between genders was noted. Among affected siblings of probands, the sex ratio, male:female, was 1.33:1, which is not significantly different from 1:1. The relative risk of developing an abdominal aortic aneurysm was 3.97 for fathers, 4.03 for mothers, 9.92 for brothers, and 22.93 for sisters.

The pedigrees were constructed of 43 patients (probands) who underwent resection of an abdominal aortic aneurysm. Seven probands (16.2%) had a first-degree relative (parent, sibling, child) known to have had an abdominal aortic aneurysm (multiplex family). To determine the prevalence of undiagnosed abdominal aortic aneurysm, ultrasound screening of first-degree relatives over age 40 years was undertaken. Of 202 eligible relatives, 103 (51.0%) were screened. An occult abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than 1.5. An incipient abdominal aortic aneurysm was defined as a clear focal bulge of the infrarenal aorta, which was less than 3.0 cm in greatest diameter. Four of 103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient abdominal aortic aneurysm (age/sex: 56M, 60M, 67F). These smaller abdominal aortic aneurysms were in patients younger than the operated probands (average age men, 67 years; women, 69 years). Six of seven individuals were in families previously considered simplex, increasing the actual multiplex family frequency from 16.2% to 27.9%. All seven new abdominal aortic aneurysms were found in the 49 siblings age 55 years or older. There were no abdominal aortic aneurysms found in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in one parent. Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and 2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the mode of inheritance of abdominal aortic aneurysm, data on first-degree relatives of 91 probands were collected. Results of segregation analysis performed on these data are reported. Many models, including nongenetic and genetic models, were compared using likelihood methods. The nongenetic model was rejected; statistically significant evidence in favor of a genetic model was found. Among the many genetic models compared, the most parsimonious genetic model was that susceptibility to abdominal aortic aneurysm is determined by a recessive gene at an autosomal diallelic major locus. A multifactorial component in addition to the major locus does not increase the likelihood of the data significantly.

Chromosomal heteromorphisms and DNA polymorphisms have been utilized to identify the mechanisms that lead to formation of human ovarian teratomas and to construct a gene-centromere map of chromosome 1 by using those teratomas that arise by meiotic nondisjunction. Of 61 genetically informative ovarian teratomas, 21.3% arose by nondisjunction at meiosis I, and 39.3% arose by meiosis II nondisjunction. Eight polymorphic marker loci on chromosome 1p and one marker on 1q were used to estimate a gene-centromere map. The results show clear linkage of the most proximal 1p marker (NRAS) and the most proximal 1q marker (D1S61) to the centromere at a distance of 14 cM and 20 cM, respectively. Estimated gene-centromere distances suggest that, while recombination occurs normally in ovarian teratomas arising by meiosis II errors, ovarian teratomas arising by meiosis I nondisjunction have altered patterns of recombination. Furthermore, the estimated map demonstrates clear evidence of chiasma interference. Our results suggest that ovarian teratomas can provide a rapid method for mapping genes relative to the centromere.

To test the null hypothesis of random segregation of marker haplotypes from an unaffected parent to affected offspring for a one-locus autosomal recessive disease, Majumder proposed a test statistic which was shown to be locally most powerful against the alternative hypothesis of non-random segregation due to linkage between the disease and marker loci. The test procedure relied on a chi-squared approximation to the null distribution of the test statistic. In the present study, we show that the chi-squared approximation is poor for most practical situations and derive the exact null distribution of a function of the test statistic. We illustrate the method using published data on tuberculoid leprosy and HLA. We show that the test procedure is invariant, and extend the method to the case of a two-locus recessive disease.

To study the genetic epidemiology of blood pressure (BP), data on 78 families were collected from a sedentary agricultural population of eastern India. The general levels of both systolic (SBP) and diastolic (DBP) blood pressures are found to be low (mean SBP = 106.41 mm Hg; mean DBP = 63.94 mm Hg). Trends of blood pressures with age are similar to those reported earlier (e.g., in the Framingham study). Environmental variables--e.g., occupation and tobacco use--do not have any direct significant effect on blood pressure variability in this population. Path analysis of family data shows a highly significant familial aggregation and yields a genetic heritability (maximum) estimate of 0.3 for both SBP and DBP. Sib-sib and mother-child correlation estimates are, respectively, 0.3 and 0.25. Father-child correlation estimates are 0.13 for SBP and near zero for DBP. A pseudopolygenic model yields the best fit to the data on SBP, while for DBP a proper resolution of various models considered could not be obtained.

Apolipoprotein C-III (APO C-III) is a structural component of very-low-density and high-density lipoprotein particles and is an inhibitor of lipoprotein lipase. In a study of genetic variation of apolipoproteins in the Mayan population of the Yucatán peninsula, we observed a quantitative polymorphism in APO C-III levels. This polymorphism is expressed as variation in immunoblot staining intensity following isoelectric focusing and as variation in plasma levels of APO C-III determined by radial immunodiffusion. This variation is consistent with the presence in Mayans of an allele associated with low levels of plasma APO C-III which we have designated APO C-III*D. Analysis of the distribution of APO C-III levels yields a gene frequency estimate for the deficiency allele of 0.59. There is a significant positive correlation between total plasma APO C-III levels and total plasma cholesterol and triglyceride levels, the lowest levels of cholesterol and triglycerides being seen in individuals homozygous for the deficiency allele. This observation is consistent with the proposed role of APO C-III in lipoprotein metabolism. Family data to determine whether this deficiency allele is due to mutation at the APO C-III structural locus were not available. However, molecular analysis using cloned probes from the APO A-I/C-III/A-IV gene cluster revealed no gross DNA rearrangement or deletion of sequences in this region in homozygous deficient individuals.

Human apolipoprotein E exhibits genetic polymorphism in all populations examined to date. By isoelectric focusing and immunoblotting, three common alleles have been demonstrated in 365 unrelated Nigerian blacks. Furthermore, the APO E genetic polymorphism's effect on quantitative levels of lipids and lipoproteins has been determined. The respective frequencies of the APO E*2, APO E*3, and APO E*4 alleles are .027, .677, and .296. The effect of APO E polymorphism is significant only on total cholesterol and low-density lipoprotein cholesterol. The average excesses of the APO E*2 allele are to lower total cholesterol and low-density lipoprotein cholesterol by 9.19 mg/dl and 11.11 mg/dl, respectively. The average excesses of the APO E*4 allele are to increase total cholesterol and low-density lipoprotein cholesterol by 5.64 mg/dl and 6.18 mg/dl, respectively. On the basis of the differences in (a) the distribution of APO E allele frequencies between the Nigerians and other populations and (b) dietary lipids, we propose a model that shows that lipid metabolism is influenced by the combined effects of the APO E polymorphism and environmental factors.

A genetical model is found to provide a good fit to family data on vitiligo. The model postulates that recessive alleles at a set of four unlinked diallelic loci are involved in the causation of the disorder. Under this multiple recessive homozygosis model, for normal X affected families ascertained through the affected parent, the expected segregation probability is .063; the estimated value is 0.53, which is not significantly different from the expected value. For normal X normal families ascertained through an affected offspring, the expected segregation probability is .037; the estimated value is .04.

From the fingertip pattern analysis of 125 families with 376 children from Velanadu Brahmin and 100 families with 286 children from Telaganya Brahmin caste sects of Andhra Pradesh, India, the occurrence of an arch on at least one of the ten finger tips is shown to be aggregated in families. The mode of aggregation is in conformity with a major dominant gene with 0.28 chance of penetrance. This is to some extent contradictory to the result published from the analysis of a single Habbanite Jewish pedigree. Some implications of this discordant result are also discussed.

With a view to estimating the effect of altitude on body dimensions vis-à-vis ethnicity-religion, geographical distance, and occupation, a comprehensive multivariate statistical analysis was performed on data pertaining to 16 anthropometric characters collected from 1,103 individuals (643 males and 460 females) belonging to two ethnic groups-Sherpa and Lepcha. Samples were drawn from several locations in the eastern Himalayan region-Darjeeling and Kalimpong in West Bengal (India), and Nepal, situated at low (1,000-2,000 meters) and high (above 3,500 meters) altitudes. The individuals sampled practice different occupations and follow different religions. Significant age and sex effects were observed. The data were age-adjusted, and sexes were treated separately. A test of equality of mean vectors indicated heterogeneity among population groups. Almost all characters were found to contribute significantly to the ability to discriminate between the groups. The overall probability of correctly classifying an individual based on body dimensions into the group in which she or he actually belongs was high (between 0.64 and 0.77). Shape and size factors could be identified that explained about 50% of the total variance and yielded a reasonable separation of the groups. Results of four different types of multivariate statistical analyses were in agreement, and showed that altitude is most highly associated with body dimensions.

Assessing the genetic causation of a disease, which is of prime importance in medical genetics, is usually done by analysing pedigree data. When gathering such data, it is often more practical to adopt a non-random sampling strategy. However, unless suitable corrections for non-random sampling are made at the time of data analysis, inferences may be grossly affected. For pedigree data ascertained through multiple probands, various correction schemes have been suggested, although the efficiencies of these schemes are unknown. This paper compares such schemes, using Monte Carlo simulation techniques, under a simple genetic model, for pedigrees of fixed sizes and structures and for probands of two types of relationship--parent-offspring, and a pair of siblings. It is found that gene frequencies are grossly overestimated and the penetrance value of heterozygotes slightly underestimated whether or not any correction for non-random sampling of pedigrees is made. Knowledge of the population value of the gene frequency improves the estimate of the penetrance parameter.

Data on 298 pedigrees, each collected through an affected proband, have been analyzed to study familial aggregation and genetics of vitiligo. The extent of familial aggregation is statistically significant at the 5% level. The disease does not appear to be inherited in a simple dominant or recessive fashion. The heritability of liability to the disease is 46% +/- 4.82%. Neither common family environment nor a major locus with additional sources (environmental and/or polygenic) can be excluded as a cause of familial aggregation. Association of the disease with six polymorphic genetic marker loci have been studied. Significant associations with ACP1 and RH loci have been found. This and earlier studies indicate that the disease is associated with genetic loci on different chromosomes, which points to a polygenic nature of the disease.

Several studies have reported association between noninsulin-dependent diabetes mellitus and GC, the vitamin D binding protein of human plasma, with the GC 1 allele in significant excess among diabetics. Additionally, there is a considerable body of animal data suggesting that vitamin D has a significant impact on insulin secretion. Examination of the insulin levels in Dogrib Indians showed that the lowest levels of fasting insulin were associated with the GC IF-IF genotype. The present study examined levels of glucose, C-peptide, and insulin at fasting and 1 hr and 2 hr following a 75 g oral glucose challenge, in a population of Hispanic-Americans and Anglos in the San Luis Valley of southern Colorado. The sample comprised a total of 468 individuals with normal glucose tolerance. Of these, 289 were Anglos and 179 were Hispanic-Americans. An analysis of covariance was performed to determine the effect of the GC genotypes on mean levels of the primary variables--glucose, C-peptide, and insulin--and a secondary variable--insulinogenic index adjusting for the covariates age, body mass index (BMI), gender, and ethnicity. The analyses revealed that there is a significant difference in mean levels of glucose at fasting (F value = 2.46; P = 0.033) among the GC genotypes in the sample. Additionally, the differences in mean levels of 1 hr postprandial glucose among the GC genotypes although not significant at a 5% level, were significant at the 10% level. No other significant phenotypic effects were observed. These analyses are not in concordance with the results of an earlier study, where lower fasting insulin was associated with the GC 1F-1F genotype.

Phenotype and gene frequencies for four blood group systems (ABO, MN, Rh and P) and haptoglobin among five endogamous groups of Delhi, India, are reported. All the systems are polymorphic in all the population groups. The average heterozygosity per locus in high (in the range 48-52 per cent) for all the groups. The extent of genic variability among the groups in terms of net codon differences per locus has been studied; the heterogeneity within the groups is large as compared to the between-group heterogeneity. There is no definite clustering of the of the groups with respect to their biological rank.

A sample of Aleuts residing in the Pribilof Islands of St. Paul (N = 163) and St. George (N = 62) and Eskimo residents of Kodiak Island (N = 294) have been typed for genetic variation at 31 discrete genetic markers. Of these, 16 were polymorphic and 15 were monomorphic. Several private polymorphisms previously reported in Eskimo or Alaskan Amerindian populations were absent in both the Aleuts and Kodiak Island Eskimos. Genetic distance analysis shows considerable genetic differentiation between Aleuts and Kodiak Island Eskimos.

For an autosomal recessive disease, a statistical procedure is developed for detecting nonrandom segregation of marker haplotypes from an unaffected parent to affected children, specifically for the case when the alternative hypothesis of linkage between the disease and marker loci is postulated. The test procedure is locally most powerful and, depending on family size and number of families sampled, any one of the three test statistics proposed can be used. An application of this procedure provides evidence of linkage between tuberculoid leprosy and HLA.

Genealogical and gene marker data from the closely related species Macaca mulatta and Macaca fascicularis have been used to search for linkage between genes coding for the blood proteins albumin, carbonic anhydrase 1 and 2, diaphorase 1 and 2, group-specific component, glucose phosphate isomerase, hemoglobin alpha chains, isocitrate dehydrogenase, prealbumin, and transferrin. The results are consistent with conservation of the linkage between the loci coding for albumin and group-specific component and loci coding for the two carbonic anhydrase isozymes, as observed in other species. Among the 38 possible pairwise comparisons, no new linkage groups were identified. Tight linkage can be excluded for most pairs of loci.

When a set of populations are compared in respect of gene frequencies, and the chi-square test of heterogeneity is found to be significant, it is pertinent to find out whether the heterogeneity can be explained by a few linear combinations of the gene frequencies, and the total heterogeneity chi-square value can be partitioned as the sum of heterogeneity chi-square values contributed by the linear combinations. The present report describes such a method, and the linear combination that explains the maximum heterogeneity is called the principal axis. An application of this method is presented to find clusters of 31 Mongoloid tribal populations of eastern India using ABO gene frequency data.

In most diseases of contemporary interest to epidemiology, the importance of familial risk factors is often assessed by relative risk measures computed from family history data. In this paper, we examine the efficiency of relative risk measures in discerning the genetic background of a disease. It is shown that even for a simple (one locus, two alleles) genetic disease, incomplete penetrance of the disease allele and/or occurrence of sporadics (i.e. non-heritable cases caused by environmental risk factors) often yields a rather small value of relative risk. This means that a small value of relative risk need not necessarily imply that genetic factors are unimportant in the aetiology of the disease. Furthermore, it is shown that the relative risk measures are complicated functions of disease gene frequency, the penetrance parameter and the sporadic rate. A rejection of genetic involvement for a disease on the basis of a single relative risk estimate may, therefore, be erroneous.

Type 2 (non-insulin-dependent) diabetes mellitus, a disease of complex aetiology, has been reported to be nonrandomly associated with several polymorphic markers in human populations. These data, plus evidence of a high prevalence of Type 2 diabetes mellitus in American Indians and mixed populations, such as Mexican-Americans, which is only partially attributable to the prevalence of obesity in these populations, makes it imperative that the nature of such associations be clarified in relation to genetic susceptibility to Type 2 diabetes mellitus. The present paper reports the results of tests of association between Type 2 diabetes mellitus and seven polymorphic markers: the blood groups - ABO, Rhesus, Duffy and Kell (K and KP) - haptoglobin and group specific component; among Anglo and Hispanic populations in the San Luis Valley of Colorado, USA. The sample population consisted of 788 individuals of which 398 were Anglo subjects (97 Types 2 diabetes mellitus patients and 301 normal individuals) and 390 Hispanic subjects (191 Type 2 diabetes mellitus patients and 199 normal individuals). Association between Type 2 diabetes mellitus and genetic markers in patients was tested using the G2 statistic within each ethnic class using normal frequencies as a comparison. Results of the tests indicated that only the Kell blood group was significantly associated with Type 2 diabetes mellitus at a 5% level among the Anglo subjects (G2 = 5.16, 1df). This significant value can be explained by chance alone, if multiple comparisons are taken into account. Our tests have not shown the previously reported haptoglobin or Rhesus blood group associations seen in Mexican-Americans in San Antonio, Texas.

Apolipoprotein D (APO D) is a constituent of plasma high-density lipoproteins. Its precise role in lipid metabolism is not well established, though it may be involved in cholesterol esterification and cholester ester transport to the liver for catabolism. No genetic polymorphism has been reported in the APO D gene product. To investigate the extent of genetic variation at the APO D structural locus, we have developed an isoelectric focusing-immunoblotting technique and have screened a large number of plasma samples from U.S. whites, U.S. blacks, Nigerian blacks, the Aleuts of the Pribilof Islands, Eskimo groups from Kodiak Island and St. Lawrence Island, and Amerindian populations from Mexico and Canada. Except for the U.S. blacks and Nigerian blacks, the APO D locus is monomorphic in all other population groups tested. In populations with black ancestry, the products of two alleles, APO D*1 and APO D*2, have been observed at respective allele frequencies .987 and .013 in U.S. blacks and .978 and .022 in Nigerian blacks. The detection of a unique protein polymorphism in blacks makes APO D a useful black marker of significance in anthropogenetics and racial admixture studies. In addition to the interindividual variation observed, APO D reveals extensive intraindividual molecular variation with a multiple banding pattern. The basis of this molecular variation is explained, in part, by variation in the number of terminal sialic acid residues. We have investigated the effect of the APO D polymorphism on triglycerides, total cholesterol, LDL-, VLDL-, HDL-, and HDL3 cholesterol in 352 Nigerian blacks (190 males and 162 females).(ABSTRACT TRUNCATED AT 250 WORDS)

In view of the many discordant findings in previous studies regarding the genetics of prelingual deafness, family data (133 nuclear families and 25 pedigrees) were gathered from India. Analysis of these data has revealed that the defect is primarily genetic, which is in agreement with earlier findings. Segregation analysis was performed to compare various autosomal diallelic one-locus and multilocus models. Our analysis revealed that the most parsimonious model for prelingual deafness is that it is controlled by recessive genes at a pair of unlinked diallelic autosomal loci. Individuals are affected if and only if they are recessive homozygous at both loci. The likelihood of the present data under this two-locus multiple recessive homozygosis model is at least 10(8) times higher than that of the one-locus models that were examined in previous studies. This model is also the best-fitting model among other plausible two-locus models.

This is the first comprehensive growth study of male children of Bengali parentage. The cross-sectional survey was undertaken in an urban high school situated in the north of the Metropolitan City of Calcutta during 1982 and 1983. The sample consisted of 815 healthy Bengali boys aged 7-16 years. In this paper, data on height, weight, and skinfold thicknesses are presented including patterns of change in these physical traits with increasing age. Mean values of height or weight of the boys--not representative for all school-going boys of Calcutta--are distinctly above the national standards given by the Indian Council of Medical Research. They are, however, shorter and lighter than the well-off boys of India but have a similar magnitude of subcutaneous fat on arm. Peak annual incremental growth in height and weight occurs in Bengali boys at 12-13 years and 14-15 years, respectively. This is about one year earlier than in the well-off Indian, British, or American boys.

An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5-fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.

Data on the distance between the birthplaces of spouses (matrimonial distance) were collected from 2,260 married individuals belonging to 21 endogamous castes of the Dhangar (shepherd) cast-cluster of Maharashtra, India. The general form of the distribution of matrimonial distances is one which is extremely positively skewed and leptokurtic. The percentage of intra-village marriages generally decreases from the southern areas of Maharashtra to the northern areas of the state, as does the inbreeding coefficient. This situation is in conformity with the socio-cultural norms regulating matrimonial choice in south and north India. An attempt has been made to relate the degree of inbreeding to the mean matrimonial distance and population size. The mean matrimonial distance is more useful in predicting the degree of inbreeding than population size.

It is shown that a simple preferential transmission of the PiZ allele by PiZ-heterozygous males for alpha 1-antitrypsin deficiency cannot maintain the observed polymorphism at the locus without invoking any viability or fertility selection against the PiZ gene carriers (heterozygotes or homozygotes). From the data on frequencies of PiZ alleles in Europe, the estimates of such selection coefficients are shown to be of the order of 5-20%, which seems too large for natural populations. Furthermore, an analysis of 26 nuclear families, each ascertained through a heterozygous PiZ or homozygous ZZ child, does not provide statistical evidence for such a hypothesis.