Suthers G K, Mulley J C, Voelckel M A, Dahl N, Väisänen M L, Steinbach P, Glass I A, Schwartz C E, van Oost B A, Thibodeau S N
Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, Australia.
Genomics. 1991 Jul;10(3):576-82. doi: 10.1016/0888-7543(91)90438-k.
The fragile X syndrome locus, FRAXA, is located at Xq27. Until recently, few polymorphic loci had been genetically mapped close to FRAXA. This has been attributed to an increased frequency of recombination at Xq27, possibly associated with the fragile X mutation. In addition, the frequency of recombination around FRAXA has been reported to vary among fragile X families. These observations suggested that the genetic map at Xq27 in normal populations was different from that in fragile X populations and that the genetic map also varied within the fragile X population. Such variability would reduce the reliability of carrier risk estimates based on DNA studies in fragile X families. Five polymorphic loci have now been mapped to within 4 cM of FRAXA--DXS369, DXS297, DXS296, IDS, and DXS304. The frequency of recombination at Xq26-q28 was evaluated using data at these loci and at more distant loci from 112 families with the fragile X syndrome. Two-point and multipoint linkage analyses failed to detect any difference in the recombination fractions in fragile X versus normal families. Two-point and multipoint tests of linkage homogeneity failed to detect any evidence of linkage heterogeneity in the fragile X families. On the basis of this analysis, genetic maps derived from large samples of normal families and those derived from fragile X families are equally valid as the basis for calculating carrier risk estimates in a particular family.
脆性X综合征位点FRAXA位于Xq27。直到最近，很少有多态性位点在遗传学上被定位到与FRAXA接近的位置。这归因于Xq27处重组频率的增加，可能与脆性X突变有关。此外，据报道FRAXA周围的重组频率在不同的脆性X家系中有所不同。这些观察结果表明，正常人群中Xq27的遗传图谱与脆性X人群中的不同，并且遗传图谱在脆性X人群中也存在差异。这种变异性会降低基于脆性X家系DNA研究的携带者风险估计的可靠性。现在已有五个多态性位点被定位到距FRAXA 4厘摩（cM）范围内——DXS369、DXS297、DXS296、IDS和DXS304。利用这些位点以及来自112个脆性X综合征家系中更远位点的数据，评估了Xq26 - q28处的重组频率。两点和多点连锁分析未能检测到脆性X家系与正常家系在重组率上有任何差异。连锁同质性的两点和多点检验未能在脆性X家系中检测到任何连锁异质性的证据。基于此分析，从正常家系大样本得出的遗传图谱和从脆性X家系得出的遗传图谱，同样可有效地作为计算特定家系携带者风险估计的基础。
