Single nucleotide polymorphisms in alcohol dehydrogenase genes among some Indian populations.

Seven ADH genes, identified until now, located in the long arm of human chromosome 4, produce seven different isozymes involved in the metabolism of ethanol to acetaldehyde. Of the more than 500 SNPs reported in the coding and non-coding regions of these genes in the world databases, 11 are more extensively studied. Three SNPs, ADH1B Arg47His (Exon3), ADH1B Arg369Cys (Exon9) and ADH1C Val349Ile (Exon8), are functionally validated in terms of phenotype-genotype correlations and are in specific linkage disequilibrium (LD) with non-coding SNPs. However, the frequency of each SNP and configuration of LD varies among populations. The Indian populations studied were conspicuous by the complete absence of African specific allele ADH1B*369Cys, the negligible frequency of East Asian specific ADH1B*47His allele and the presence of a novel SNP ADH1B A3529G (Intron3). The ADH1C*349Ile was the only functional allele polymorphic with a strong LD block in all the populations studied and the high F(st) value observed for the non-coding ADH1B Rsa1 variant was in conformity with world populations.     

Neurological aspects of del(1q) syndrome

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions.     

A genetic study of hyper-alpha-lipoproteinemia

Because of its association with longevity and reduced incidence of coronary heart disease, it becomes important to find out how elevated HDL-cholesterol levels are determined. Analyses of family data from Cincinnati initially suggested environmental factors common to sibs; however, some form of dominant inheritance could not be ruled out. Reanalysis of the Cincinnati data by Iselius and Lalouel concluded against a major locus, but did identify three families as possibly segregating for a major locus. Analysis of an additional 26 kindreds from the same population in Cincinnati by Siervogel and associates concluded that a major gene could be causing familial aggregation of high density lipoprotein in white kindreds. In this analysis, we pooled all the white Cincinnati kindreds (n = 31), and investigated the familial transmission using complex segregation analysis. We failed to obtain clear evidence for major locus determination. Under the parsimonious hypothesis of no major locus, the polygenic heritability and common sibling environmental correlation were estimated as 0.531 and 0.263, respectively, consistent with other evidence.     

Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects

Subcortical structural changes have been reported to occur in some elderly subjects with late age onset depression. Given the association between diseases affecting subcortical structures and affective disorders, this suggests that these structural changes may be involved in the etiology of late age onset depression in some patients. With the advent of Brain Magnetic Resonance Imaging (MRI), "in vivo" analysis of these subcortical structures is now possible. The authors report a higher occurrence of caudate (60% vs. 11%) and large deep white matter hyperintensities (60% vs. 11%) in late age onset elderly depressed subjects compared with early onset elderly depressed subjects. These results suggest that late age onset depression may be mediated by caudate and white matter structural changes in some patients.     

Somatomedin production and response to mitogen by lymphocytes in children with growth hormone deficiency

Studies on the lymphocyte proliferative activity of the sera from growth hormone (GH) deficient patients have resulted in contradictory observations. The ability of lymphocytes to synthesize somatomedin-C (Sm-C) and thus account for a normal proliferative activity (previously observed by us) of the GH-deficient sera was studied, by measuring Sm-C concentration in the culture medium using a standard radioimmunoassay for Sm-C. The response of lymphocytes to the mitogen phytohemagglutinin (PHA), as determined by the incorporation of 3H thymidine into DNA, was also studied. The Sm-C concentrations in the cultures reflected the Sm-C concentrations of the respective serum added and did not alter with significant increases in the cell number induced by PHA. The lymphocytes from GH-deficient children and normal children were indistinguishable in their ability to respond to PHA. We conclude that lymphocyte proliferation in short-term culture, was not associated with an increase in Sm-C and that in the lymphocyte proliferation assay the sera and the lymphocytes from GH-deficient children respond similarly to the sera and lymphocytes from normal children.     

Clonal chromosomal abnormalities in hemangiopericytoma

We report the cytogenetic findings in nine hemangiopericytomas studied after short-term culture. Clonal chromosome abnormalities were present in four cases. One case had a simple translocation (12;19)(q13;q13.3) as the sole abnormality whereas complex and multiple chromosomal abnormalities involving almost all chromosomes in the complement characterized tumors from the three other cases.