👤 M C Smart

Studies have consistently demonstrated that variants in a number of candidate genes are significant determinants of lipid levels in adults. However, few studies have investigated the impact of these variants in children. Therefore, in the present investigation we examined the influence of ten common variants in the genes for lipoprotein lipase (LPL-S447X), cholesterol ester transfer protein (CETP-Taq1B) apolipoprotein (APO) E (epsilon2, epsilon3, epsilon4), APOA5 (-1131C>T and S19W), APOA4 (S347T) and APOC3 (-482C>T; 1100C>T and 3238G>C) on lipoprotein levels children from the Gene-Diet Attica Investigation on childhood obesity (GENDAI). The ten variants selected were genotyped in 882 Greek children, mean age: 11.2+/-0.7 years (418 females and 464 males). Genotypes were assessed using TaqMan technology. Significantly higher total cholesterol (TC) (p=0.0001) and low-density lipoprotein cholesterol (LDL-C) (p<0.0001) were observed in APOE epsilon4 carriers compared to epsilon3/epsilon3 homozygotes and epsilon2 carriers. The association of APOE genotype with TC and high-density lipoprotein cholesterol (HDL-C) ratio (p=0.0008) was further modulated by body mass index. Carriers of the CETP TaqIB B2 allele had significantly higher HDL-C (p<0.0001) and significantly lower TC: HDL-C ratio (p<0.0001) compared to B1/B1 individuals. No significant associations were observed between APOA4, APOA5 and APOC3 variants and serum lipids. This study demonstrates that these common variants are associated with lipid levels in this healthy paediatric cohort, suggesting that even in these young children there may be potential in predicting their lifelong exposure to an adverse lipid profile. Show less

The classical recessive coat color mutation misty (m) arose spontaneously on the DBA/J background and causes generalized hypopigmentation and localized white-spotting in mice, with a lack of pigment on the belly, tail tip, and paws. Here we describe moonlight (mnlt), a second hypopigmentation and white-spotting mutation identified on the C57BL/6J background, which yields a phenotypic copy of m/m coat color traits. We demonstrate that the 2 mutations are allelic. m/m and mnlt/mnlt phenotypes both result from mutations that truncate the dedicator of cytokinesis 7 protein (DOCK7), a widely expressed Rho family guanine nucleotide exchange factor. Although Dock7 is transcribed at high levels in the developing brain and has been implicated in both axon development and myelination by in vitro studies, we find no requirement for DOCK7 in neurobehavioral function in vivo. However, DOCK7 has non-redundant role(s) related to the distribution and function of dermal and follicular melanocytes. Show less