Cancer genetics

MLL translocations specify a distinct gene expression profile that distinguishes a unique leukaemia. Armstrong, S. A. et al. Nature Genet. 10.1038/ng765 (2001) [PubMed]

Some patients with acute lymphoblastic leukaemia (ALL) carry translocations in the mixed-lineage leukaemia (MLL) gene and have a very poor prognosis. Because MLL regulates the expression of HOX genes, which function in haematopoiesis, the authors investigated whether MLL translocations alter HOX gene expression to assess a role for these genes in the disease. Using microarray expression profiling, they surprisingly found that MLL patients have a highly uniform and distinct gene-expression profile, different from that of ALL or acute myelogenous leukaemia patients, indicating that MLL might be a distinct disease.

Epigenetics

Dnmt3L and the establishment of maternal genomic imprints. Bourc'his, D. et al. Science, 22 November 2001 (10.1126/science.1065848) [PubMed]

Bourc'his et al. knocked out the DNA methyltransferase Dnmt3L in mice to investigate its role in establishing and maintaining genomic imprints. They found that heterozygous progeny from Dnmt3−/− females die before mid-gestation with developmental and placental defects. Furthermore, Dnmt3L+/− embryos derived from homozygous mutant oocytes lack maternal imprints, causing genes that are normally expressed from only the paternal allele to be biallelically expressed. Genome-wide methylation levels were otherwise normal, indicating that Dnmt3L is the first known gene to be essential for the de novo methylation of single-copy sequence. In addition, its sequence indicates that it is more likely to act as a regulator of methylation at imprinted loci than as a DNA methyltransferase.

Population genetics

Female sticklebacks count alleles in a strategy of sexual selection explaining MHC polymorphism. Reusch, T. B. H. et al. Nature 414, 300–302 (2001) [PubMed]

Many theories have been proposed to explain the polymorphism of major histocompatibility complex (MHC) genes, which are important in vertebrate immunity. This report states that, contrary to previous studies in human and mice, which indicated that females select mates with an MHC complement most dissimilar to their own to avoid the consequences of inbreeding, female sticklebacks prefer males with the largest number of different MHC loci. Maximizing the number of MHC alleles in offspring presumably increases their fitness by boosting resistance to parasites. The authors suggest that two non-exclusive strategies exist to maintain MHC polymorphism in vertebrates: inbreeding avoidance and parasite resistance.