Sarfarazi M, Wijmenga C, Upadhyaya M, Weiffenbach B, Hyser C, Mathews K, Murray J, Gilbert J, Pericak-Vance M, Lunt P
Department of Pediatrics, University of Connecticut Health Center, Farmington 06030.
Am J Hum Genet. 1992 Aug;51(2):396-403.
Members of an international consortium for linkage analysis of the facioscapulohumeral muscular dystrophy (FSHD) gene have pooled data for joint analyses, in an attempt to determine the precise location of the FSHD gene and the order of four DNA markers on 4q35 region. Six laboratories determined a total of 3,078 genotypes in 65 families, consisting of a total of 504 affected subjects and 559 unaffected subjects. For each marker, a mean of 648 meioses were informative. D4S139 and D4S163 were identified as the closest linked markers to the FSHD locus, with 99% upper confidence intervals of recombination fractions of .08 and .10, respectively. We have used the CRI-MAP program to construct the most likely order of cen-D4S171-F11-D4S163-D4S139-FSHD-tel, with favorable odds of 10(8)-10(114) over all other orders except that in which F11 and D4S171 are reversed, for which the odds ratio was 191:1. With this order, the genetic map of this region extends 25.5 cM in males and 13.8 cM in females (averaging 19.5 cM for sexes combined); the sex difference was statistically significant (P = .0013). Comparison between families for the two-point and multipoint lod scores involving FSHD showed no evidence for heterogeneity of this disorder. However, after the completion of this analysis, one large family which might show heterogeneity was identified. In view of this and the fact that all of the linked markers reside on the same side of the FSHD locus, the clinical application of these markers is not recommended at this time.
一个国际财团的成员对面肩肱型肌营养不良症（FSHD）基因进行连锁分析，他们汇总数据进行联合分析，试图确定FSHD基因的精确位置以及4q35区域上四个DNA标记的顺序。六个实验室在65个家庭中确定了总共3078个基因型，其中共有504名受影响的受试者和559名未受影响的受试者。对于每个标记，平均有648个减数分裂具有信息性。D4S139和D4S163被确定为与FSHD基因座最紧密连锁的标记，其重组率的99%置信区间上限分别为0.08和0.10。我们使用CRI-MAP程序构建了最可能的顺序：着丝粒-D4S171-F11-D4S163-D4S139-FSHD-端粒，与所有其他顺序相比，其优势比为10（8）-10（114），除了F11和D4S171顺序颠倒的情况，其优势比为191:1。按照这个顺序，该区域的遗传图谱在男性中延伸25.5厘摩，在女性中延伸13.8厘摩（两性平均为19.5厘摩）；性别差异具有统计学意义（P = 0.0013）。对涉及FSHD的两点和多点连锁分数在家庭之间进行比较，没有发现这种疾病存在异质性的证据。然而，在这项分析完成后，发现了一个可能显示异质性的大家庭。鉴于此以及所有连锁标记都位于FSHD基因座同一侧的事实，目前不建议临床应用这些标记。
