Biomedical subjects
Publications and source records attributed to M R Srinivasan.
The problem of estimation of variance components based on diallel model for unbalanced data has been addressed. The least squares approach to quadratic estimation has been adopted in obtaining the explicit solutions for the design and genetic components of variance.
The aim of this work was to explore the influences of the shared familial environment and the nonshared individual environment on body mass index in light of convincing evidence for genetic influence. A cross-sectional adoption design was used, including information on adult adoptees and their biological fathers and mothers, biological full siblings and paternal and maternal half siblings, and adoptive fathers and mothers. Body mass index (weight/height2) was derived from reported height and weight. A model of familial resemblance based on path analysis is used to test for effects of genetic influence and for effects of the environment shared among family members: transmission from the adoptive father and adoptive mother to the adoptee, from biological father and biological mother to biological children they reared, from the biological father to maternal half-siblings, from the biological mother to paternal half-siblings, and among biological siblings who may have lived together. The model also incorporates effects of assortative mating of the biological parents and of the adoptive parents, of shared preadoptive environmental influences between the biological mother and the adoptee, and of selective placement of the adoptee. The estimated heritability was 0.34 (standard error 0.03). No parameter indicating effects of shared familial environment either before or after adoption, assortative mating, or selective placement was significant. There was strong evidence for genetic effects, and no evidence for any effects related to the shared family environment--all familial resemblance in adults can be attributed to genetic influences. However, more than half of the interindividual differences in body mass index is due to nonshared individual environmental influences.
Dried flower of A. alliaceum when fed at 2% level in diet for 6 weeks to experimental rats rendered hypercholesterolemic by cholesterol feeding, exhibited blood cholesterol lowering effect. Cholesterol lowering efficacy of these garlic smelling flowers was similar to garlic oil fed at 0.002% level. Animals fed A. alliaceum flowers excreted higher amounts of neutral and acidic sterols in faeces similar to onion or asafoetida fed (at 2% dietary level) rats. A. alliaceum significantly lowered the absorption of dietary cholesterol from intestine like other sulfur containing spices, viz. garlic oil, onion and asafoetida. It is inferred from this study that limitation in intestinal cholesterol absorption is responsible for cholesterol lowering effect of this flower in hypercholesterolemic animals.
Forensic applications of DNA typing data require the estimation of the frequencies of all observed alleles, which is currently done by a fixed set of groupings (binning) of alleles in a database. Recently it's validity has been questioned on the ground that when a DNA fragment size is close to a bin boundary, the frequencies of all adjacent bins should be added. On the contrary, the current forensic database indicates that when the match window of a DNA fragment overlaps 2 bins, it is enough to consider the bin with the larger frequency, and this never underestimates the frequency within the match interval with the current choice of fixed-bin widths. On average, the current fixed-bin procedure yields an allele frequency at least 2-fold higher than that of a floating-bin.
Nonparametric measures of correlations of DNA fragment lengths within and between variable number of tandem repeat (VNTR) loci are proposed to test the hypothesis of random association of allele sizes at VNTR loci. Transformations of these nonparametric correlation measures are suggested to detect deviations of their null expectations caused by population subdivision and errors of measurement of VNTR fragment lengths. Analytic and permutation-based computer simulation studies are performed to show that under the hypothesis of independence of allele sizes the transformed correlation measures are normally distributed, irrespective of the VNTR fragment size distribution in the population even when the number of individuals samples is as low as 100. Power calculations are performed to establish that the current population data on six VNTR loci in the US Hispanic sample are in accordance with the hypothesis of random association of allele sizes within and between loci. Implications of these results in the context of forensic use of DNA typing are also discussed.
Multilocus genotype probabilities, estimated using the assumption of independent association of alleles within and across loci, are subject to sampling fluctuation, since allele frequencies used in such computations are derived from samples drawn from a population. We derive exact sampling variances of estimated genotype probabilities and provide simple approximation of sampling variances. Computer simulations conducted using real DNA typing data indicate that, while the sampling distribution of estimated genotype probabilities is not symmetric around the point estimate, the confidence interval of estimated (single-locus or multilocus) genotype probabilities can be obtained from the sampling of a logarithmic transformation of the estimated values. This, in turn, allows an examination of heterogeneity of estimators derived from data on different reference populations. Applications of this theory to DNA typing data at VNTR loci suggest that use of different reference population data may yield significantly different estimates. However, significant differences generally occur with rare (less than 1 in 40,000) genotype probabilities. Conservative estimates of five-locus DNA profile probabilities are always less than 1 in 1 million in an individual from the United States, irrespective of the racial/ethnic origin.
Recent attempts to detect mutations involving single base changes or small deletions that are specific to genetic diseases provide an opportunity to develop a two-tier mutation-screening program through which incidence of rare genetic disorders and gene carriers may be precisely estimated. A two-tier survey consists of mutation screening in a sample of patients with specific genetic disorders and in a second sample of newborns from the same population in which mutation frequency is evaluated. We provide the statistical basis for evaluating the incidence of affected and gene carriers in such two-tier mutation-screening surveys, from which the precision of the estimates is derived. Sample-size requirements of such two-tier mutation-screening surveys are evaluated. Considering examples of cystic fibrosis (CF) and medium-chain acyl-CoA dehydrogenase deficiency (MCAD), the two most frequent autosomal recessive disease in Caucasian populations and the two most frequent mutations (delta F508 and G985) that occur on these disease allele-bearing chromosomes, we show that, with 50-100 patients and a 20-fold larger sample of newborns screened for these mutations, the incidence of such diseases and their gene carriers in a population may be quite reliably estimated. The theory developed here is also applicable to rare autosomal dominant diseases for which disease-specific mutations are found.
The influence of vanillin (0.15 mg %) and capsaicin (0.3 mg %) on liver and blood lipids in growing female Wistar rats was determined, when fed along with a normal diet. Vanillin, like capsaicin, decreased the serum triglycerides and the triglycerides associated with lipoproteins viz., VLDL+LDL and HDL with a tendency to lower liver triglycerides as well. Cholesterol and phospholipids in liver and serum were unaffected. The accumulation of triglycerides in serum after Triton WR-1339 blocking was higher in animals fed a vanillin supplemented normal or hypertriglyceridemic diet than in the corresponding controls. The accumulation of triglycerides in serum with capsaicin supplementation with either diet was much higher than with vanillin supplementation.
A synthetic analogue of capsaicin (0.2 mg%) fed to female Wistar rats along with a high fat diet for 11 weeks, lowered adipose tissue weight and also liver and serum triglycerides. The compound elevated total post heparin plasma lipase and skeletal muscle lipase activities. The increase in the latter indicates the possible mechanism by which capsaicin enhances serum triglyceride uptake by muscle tissue and in turn lowers triglyceride levels. A single dose of capsaicin even at a much higher level failed to lower serum triglycerides emphasizing the necessity of continuous ingestion of capsaicin for exerting its hypolipidemic effect.
The coronary arteries of the goat heart were studied using angiographic techniques and molds of the coronary vessel trees. Blood supplies to the left and right ventricles, interventricular septum, atrioventricular node, and apex of the caprine heart were studied. The goat possesses a left dominant pattern of coronary supply with relatively uniform coronary anatomy and may provide a good large animal model for testing cardiovascular assist devices.