Xq27-q28区域新限制性片段长度多态性的基因定位

Genetic mapping of new RFLPs at Xq27-q28.

作者信息

Suthers G K, Oberlé I, Nancarrow J, Mulley J C, Hyland V J, Wilson P J, McCure J, Morris C P, Hopwood J J, Mandel J L

机构信息

Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, South Australia.

出版信息

Genomics. 1991 Jan;9(1):37-43. doi: 10.1016/0888-7543(91)90218-4.

DOI:10.1016/0888-7543(91)90218-4

PMID:1672291

Abstract

The development of the human gene map in the region of the fragile X mutation (FRAXA) at Xq27 has been hampered by a lack of closely linked polymorphic loci. The polymorphic loci DXS369 (detected by probe RN1), DXS296 (VK21A, VK21C), and DXS304 (U6.2) have recently been mapped to within 5 cM of FRAXA. The order of loci near FRAXA has been defined on the basis of physical mapping studies as cen-F9-DXS105-DXS98-DXS369-DXS297-FRAXA-++ +DXS296-IDS-DXS304-DXS52-qter. The probe VK23B detected HindIII and XmnI restriction fragment length polymorphisms (RFLPs) at DXS297 with heterozygote frequencies of 0.34 and 0.49, respectively. An IDS cDNA probe, pc2S15, detected StuI and TaqI RFLPs at IDS with heterozygote frequencies of 0.50 and 0.08, respectively. Multipoint linkage analysis of these polymorphic loci in normal pedigrees indicated that the locus order was F9-(DXS105, DXS98)-(DXS369, DXS297)-(DXS293,IDS)-DXS304-DXS52. The recombination fractions between adjacent loci were F9-(0.058)-DXS105-(0.039)-DXS98-(0.123)-DXS369-(0.00)- DXS297-(0.057)-DXS296- (0.00)-IDS-(0.012)-DXS304-(0.120)-DXS52. This genetic map will provide the basis for further linkage studies of both the fragile X syndrome and other disorders mapped to Xq27-q28.

摘要

由于缺乏紧密连锁的多态性位点，位于Xq27的脆性X突变（FRAXA）区域的人类基因图谱的绘制工作受到了阻碍。多态性位点DXS369（由探针RN1检测）、DXS296（VK21A、VK21C）和DXS304（U6.2）最近已被定位到距FRAXA 5厘摩（cM）以内。基于物理图谱研究，已确定FRAXA附近位点的顺序为：着丝粒-F9-DXS105-DXS98-DXS369-DXS297-FRAXA-++ +DXS296-IDS-DXS304-DXS52-染色体末端。探针VK23B在DXS297处检测到HindIII和XmnI限制性片段长度多态性（RFLP），杂合子频率分别为0.34和0.49。一个IDS cDNA探针pc2S15在IDS处检测到StuI和TaqI RFLP，杂合子频率分别为0.50和0.08。在正常家系中对这些多态性位点进行的多点连锁分析表明，位点顺序为F9-（DXS105，DXS98）-（DXS369，DXS297）-（DXS293，IDS）-DXS304-DXS52。相邻位点之间的重组率为F9-（0.058）-DXS105-（0.039）-DXS98-（0.123）-DXS369-（0.00）-DXS297-（0.057）-DXS296- （0.00）-IDS-（0.012）-DXS304-（0.120）-DXS52。这一遗传图谱将为脆性X综合征以及定位到Xq27 - q28的其他疾病的进一步连锁研究提供基础。