Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = -0.

Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2.

Background: Hereditary Spastic Paraplegia (HSP) represents a large group of clinically and genetically heterogeneous disorders linked to over 70 different loci and more than 60 recognized disease-causing genes. A heightened vulnerability to disruption of various cellular processes inherent to the unique function and morphology of corticospinal neurons may account, at least in part, for the genetic heterogeneity.

Methods: Whole exome sequencing was utilized to identify candidate genetic variants in a four-generation Siberian kindred that includes nine individuals showing clinical features of HSP.