Animal models

Identification and functional analysis of mutation in the hypocretin (orexin) genes of narcoleptic canines. Hungs, M. et al. Genome Res. 11 , 531–539 (2001) [PubMed]

In dobermans and labradors, familial narcolepsy is caused by mutations in hypocretin receptor 2 (Hcrtr2), but most familial and sporadic cases of human narcolepsy lack mutations in hypocretin (Hcrt) and its receptors. In this study of the dog Hcrtr2 and Hcrt loci in familial and sporadic cases of canine narcolepsy, only one further mutation was identified. The lack of mutations at these genes in sporadic cases indicates that this form of narcolepsy is genetically heterogeneous in dogs, as it is in humans.

Human genetics

Neuronal sodium-channel α1 subunit mutations in generalized epilepsy with febrile seizures plus. Wallace, R. H. et al. Am. J. Hum. Genet. 68 , 859–865 (2001) [PubMed]

A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus — and prevalence of variants in patients with epilepsy. Escayg, A. et al. Am. J. Hum. Genet. 68 , 866–873 (2001) [PubMed]

Generalized epilepsy with febrile seizures plus (GEFS+) is a syndrome that shows genetic heterogeneity and a highly variable phenotype. Some cases of GEFS+ are caused by mutations that affect subunits of a sodium channel (SCN1A and SCN1B), and lead to reduced channel inactivation and increased neuronal excitability. To test whether SCN1A mutations could cause more common forms of epilepsy, Escayg et al. screened 226 patients with a range of phenotypes. Several variants of the SCN1A gene were identified, but functional studies will be needed to test their relevance. Meanwhile, by screening a further 36 GEFS+ families, Wallace et al. show that the sodium-channel defects could account for ∼17% of familial cases. Overall, sodium-channel defects are an important cause of some forms of epilepsy, and these studies will encourage the analysis of genes that encode other sodium-channel subunits or interacting proteins.

Human disease

A major susceptibility locus for leprosy in India maps to chromosome 10p13. Siddiqui, M. R. et al. Nature Genet. 27 , 439–441 (2001) [PubMed]

Half of the world's 800,000 cases of leprosy — a chronic infectious disease that is caused by the pathogenic bacterium Mycobacterium leprae — occur in India. A genetic linkage scan of affected sib-pairs, from 224 families in South India with 396 microsatellite markers, revealed a significant linkage of a major susceptibilty locus to markers on chromosome 10p13. This study proves that genome-wide linkage analysis can be used to identify major loci even in cases, such as this, in which the genetic component to susceptibility would be expected to be highly polygenic.