A SPG3A mutation with a novel foot phenotype of hereditary spastic paraplegia in a Chinese Han family

Hereditary spastic paraplegia （HSP） （MIM#182600） is a group of heterogeneous neurodegenerative disorders, with 35 underlying loci recognized by the HGNC （HUGO Gene Nomenclature Committee; http：//www.gene.ucl.ac.uk/nomenclature/） and 10 identified genes （ http ： //www. gene. ucl. ac. uk/cgi-bin/nomenc lature/ searchgenes.pl plus NIPA1, last search July 2006）. The mode of inheritance may be autosomal dominant, autosomal recessive or X-linked. Among these, autosomal dominant spastic paraplegia （AD-HSP） is the most common type, accounting for 70%-80% of all families. The disease is characterized by lower limb spasticity, hyperreflexia, progressive spastic gait and an extensor plantar response. Pes cavus is one of the commonly reported foot phenotypes.

High resolution linkage disequilibrium and haplotype maps for the genes in the centromeric region of chromosome 15 in Tibetans and comparisons with Han population

Genetic variations and their functional implications have been one of the focuses in recent genome research. With the release of the HapMap by the International Consortium, and the availability of the ultra-high-volume genotyping platform, it will soon be possible to use genome-wide association ap- proach to identify genetic variations responsible for complex traits/diseases. While the power of this ap- proach is generally agreed, it is a debated issue as to how much population difference should be exploited, and how best it should be applied. To address this issue we have sequenced 7 genes in the centromeric region of chromosome 15, investigated their SNPs, SNP frequencies, tagSNPs, LD structures, and hap- lotypes in 50 Tibetan subjects, and compared them with those from the Han population. Genetic diversi- ties between the two populations were also quantified. Our results show that the overall genetic variation between the two populations is very little, but there are differences, primarily in allele frequencies, which is a dominating factor for haplotypes and tagSNPs. In general Tibetans have longer LD and less diversity inthe region studied. These data provide genetic evi- dence for the close relationship between the two populations, and support the idea that all populations are fundamentally the same, but also indicate popu- lation variations, particularly in allele frequency, should be taken into account in complex traits/ dis- eases analysis. Data obtained in this investigation not only help us understand the genome region, but also provide road maps for variation study in the genes/ region in Tibetan population.