Comparative genomics

A genetic linkage map of the baboon ( Papio hamadryas ) genome based on human microsatellite polymorphisms. Rogers, J. et al. Genomics 67 , 237–237 (2000).

This is the first non-human primate linkage map, in which 694 baboons were genotyped for 325 human and six novel baboon microsatellite markers across all 20 baboon autosomes. Locus order on seven human chromosomes was found to be conserved when the baboon and human maps were compared, and centiMorgan distances indicate that recombination rates are higher in humans than in baboons.

Disease model

A novel genetic pathway for sudden cardiac death through defects in the transition between ventricular and conduction system cell lineages. Nguyen-Tran, V. T. B. et al. Cell 102 , 671–682 (2000).

By inactivating HF-1b, a transcription factor gene that is preferentially expressed in the heart, these researchers generated the first mouse model of sudden cardiac death. Although the mutant mice survive to term and their hearts develop and function normally, they die suddenly at 1–6 months of age from ventricular arrhythmias. The altered expression patterns of conduction system-specific markers indicate that cells of the ventricular muscle and conduction system fail to differentiate with normal electrophysiological properties.

Association studies

The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Altshuler, D. et al. Nature Genet. 26 , 76–80 (2000).

The authors evaluated 16 published genetic associations to type 2 diabetes. Only one significant association to a decreased risk of diabetes type 2 was confirmed. This was with a common Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ gene, which encodes a nuclear hormone receptor that regulates adipogenesis. The common proline allele has a modest effect on individual risk but influences up to 25% of type 2 diabetes in the population.

Human mutation rate

Estimate of the mutation rate per nucleotide in humans. Nachman, M. W. et al. Genetics 156 , 297–304 (2000).

This paper provides a precise estimate of the rates and patterns of human mutations at the nucleotide level (reviewed in this issue by Jim Crow). By sequencing 18 processed pseudogenes in humans and chimpanzees, the authors estimate that 175 new mutations occur per generation, with mutations at CpG dinucleotides occurring ten times more frequently than at other sites. The mutation rate in males is four times higher than that of females, but no differences were seen between sex chromosomes and autosomes.