Dietz J N, Robbins T, Cannon L A, Schwartz C E, Carey J C, Johnson J P, Kivlin J, Skolnick M H
Genet Epidemiol. 1986;3(5):313-21. doi: 10.1002/gepi.1370030504.
This report describes a study that examines the hypotheses of genetic linkage between the autosomal dominant disorder neurofibromatosis (NF) and loci on human chromosomes 4 and 19. Twelve Utah families were evaluated for evidence of possible linkage of NF to six known markers on chromosome 4 and five markers on chromosome 19. Due to previous reports suggesting tight linkage of NF to the GC locus on chromosome 4 and the C3 (linked to myotonic dystrophy) locus on chromosome 19, these two markers were of particular interest. For the Utah families the cumulative LOD score for GC was -4.81 (r = 0.05). Cumulative LOD scores were -0.90 (r = 0.05) and -1.01 (r = 0.05) for C3 serum determinations and a C3 DNA polymorphism respectively. Linkage data is also included on all individual informative families for the GC and C3 loci to specifically address the question of heterogeneity. Linkage data is consistent with, but does not strongly support, the existence of heterogeneity implicating both the GC locus on chromosome 4 and the C3 locus on chromosome 19. A compilation of cumulative LOD scores from this and other current linkage studies produces values that in the absence of heterogeneity refute previous reports for tight linkage of NF to GC and to C3.
本报告描述了一项研究，该研究检验了常染色体显性疾病神经纤维瘤病（NF）与人类4号和19号染色体上基因座之间的遗传连锁假说。对12个犹他州家庭进行了评估，以寻找NF与4号染色体上6个已知标记及19号染色体上5个标记之间可能存在连锁的证据。由于先前的报告表明NF与4号染色体上的GC基因座以及19号染色体上的C3（与强直性肌营养不良相关）基因座紧密连锁，所以这两个标记格外令人关注。对于犹他州的家庭，GC基因座的累积对数优势计分（LOD）为-4.81（r = 0.05）。C3血清测定和C3 DNA多态性的累积LOD计分分别为-0.90（r = 0.05）和-1.01（r = 0.05）。还纳入了所有GC和C3基因座信息丰富的个体家庭的连锁数据，以专门解决异质性问题。连锁数据与4号染色体上的GC基因座和19号染色体上的C3基因座存在异质性这一观点相符，但并不强力支持该观点。汇总本研究及其他当前连锁研究的累积LOD计分后得出的数值，在不存在异质性的情况下，反驳了先前关于NF与GC及C3紧密连锁的报告。
