Gene expression

Random monoallelic expression of three genes clustered within 60 kb of mouse t complex genomic DNA. Sano, Y. et al. Genome Res. 15, 1833–1841 (2001) [PubMed]

There are three mechanisms of gene-dosage control in mammals: random X inactivation, parent-of-origin autosomal gene imprinting and random autosomal inactivation. This last is very rare, but Sano et al. now report a cluster of three genes — Nubp2, Igfals and Jsap1 — on mouse chromosome 17 that undergo this process. In single cells, these genes show X-like, random monoallelic expression, but can switch between active and inactive states during cell division — monoallelic expression correlates with the 50% methylation status of the genomic region. The authors discuss possible mechanisms for such gene expression patterns and their involvement in the biology of the t complex.

Human genetics

An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Pennacchio, L. A. et al. Science 294, 169–173 (2001) [PubMed]

Apolipoproteins are known to affect plasma lipid levels in humans — an important factor in susceptibility to heart disease. Pennacchio et al. explored the already known apolipoprotein gene cluster on chromosome 11 for new susceptibility loci. By comparing mouse and human sequence, they identified a new locus, which when knocked out in mice leads to a substantial increase in plasma lipid levels, but when overexpressed causes these levels to drop below wild-type levels. This marked effect prompted the authors to look for SNPs in the human locus — all three rare alleles that they studied were associated with high lipid levels.

Development

Reciprocal mouse and human limb phenotypes caused by gain- and loss-of-function mutations affecting Lmbr1. Clark, R. M. et al. Genetics 159, 715–726 (2001) [PubMed]

Most of the dominantly inherited preaxial polydactly and syndactyly phenotypes, which affect limb-digit number, map to human chromosome 7q36 and to a homologous region in mice. By using deletion chromosomes, these authors show that limb defects that map to this region in mice result from gain-of-function mutations, rather than by haploinsufficiency. Mice with loss-of-function mutations in limb region 1 (Lmbr1), which might be allelic to the known limb morphology mutants Hemimelic extra toes and Hammertoe, have fewer limb digits than normal. Because this phenotype is reciprocal to polydactly, the authors propose that levels of Lmbr1 activity control the morphology of the vertebrate limb skeleton.