Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus.
Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials.
Nikali
K
K
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Suomalainen
A
A
Terwilliger
J
J
Koskinen
T
T
Weissenbach
J
J
Peltonen
L
L
D017668:Age of Onset; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D013132:Spinocerebellar Degenerations / Q000145:classification / Q000453:epidemiology / Q000235:genetics*
D005819:Genetic Markers