先天性白内障一家系全基因组扫描基因定位及候选基因序列分析.pdfVIP

.919. ·调聋研究· 先天性白内障一家系全基因组扫描基因定位及 候选基因序列分析 布娟杨建军李宁东杨永佳赵堪兴 Linkage analysis of a Chinese family with congenital cataract and mutation screening of BFSPl Bu Juαn ， Y.αng Jiαnjun ,Li Ningdong , y，αng Yongjiα ， Zhαo K，αnxing. Thírd Hospital 0/ Peking University , Beijing 100191 ,China Abstract Objectlve Congenítal cataract ís one of the major 口auses of blíndness ín human beíng , and gene 8tudy on congenítal cataract ís helpful to understand its pathogenesís. Thís study was to ìdentify the genetic location of the candidate gene by linkage analysis and describe the c1inical phenotype in a Chínese family with autosomal dominant congenital cataract ( ADCC) . Methods Sixteen patients with ADCC and 26 normal subjects were collected from a Chinese famíly. A detailed clínical examination was performed for the family members. The genomíc DNA of all family members was extracted from peripheral blood leukocytes. Linkage analysis and genome-wide linkage screening was conducted using fluorescent detection of 370 mìcrosatel1ite markers representing all auto例mes at an average resolutíon of approxímately 10 cm. The polymerase chain reactions were 侃而ed out to amplify all 370 microsatellite markers. The allele sizes were determined on ABI 3130-avant genetìc analysís according to an intemal size standard and the results were analyzed using Genescan 3. 1 and Genotyper 2.0 software. Multipoint LOD 8cor制 between the disease status and the marker alleles were calculated using the Linkage software package of Sim Walk 2 , Version 3. 35. Directly sequence wωconducted on affected members of thís family to determine the mutation in all exons of BFSPl gene. The study followed the Helsinki Statement. Results The affected members in the family were bom with classic phenotype of zonular ADCC. Linkage analysis showed the markers D20S163 , D20S915 , D20S152 , D20日98 ， D20S904 ， D20S875 ， D20S112 ,D20S1l40 , D20S432 co-segregated wìth the disease locus in all affected members. The maxímu