LINKAGE STUDIES IN NEUROFIBROMATOSIS

神经纤维瘤病是一种常见的人类常染色体显性遗传病 以咖啡色斑点、神经纤维瘤和广泛的 其他表现形式。它的高自发突变率(在 在人类中描述的最高)和利用蛋白质的初步连锁分析 多态现象表明，导致突变的原因可能是 不同家族中的不同基因座。 连锁分析识别突变基因位置的能力 最近由于引入了DNA多态，如 遗传标记，这应该允许任何疾病基因在以下情况下被定位 有合适的家庭可供研究，如果有足够数量的家庭 可以生成信息性标记。Nf是一个非常合适的目标 这种方法带来了混乱。 我们建议确定三到四个患有神经营养不良的三代或四代家庭 有足够的可用的家庭成员，以允许对单个成员进行连锁分析 这样，潜在的基因座异质性不会破坏任何 联想。使用EB病毒转化的淋巴细胞，我们将寻找 与GC血型相关的证据(CHR。4)和分泌物(Chr.19)两者都有 其中一些基因被认为与NF有关联，但不是全部 家人。我们还将开发和研究8号染色体上的标记(其中 间接证据表明，核因子基因座可能是， 探测器无论如何都是需要的)。我们将最大限度地提高获得 通过使用探针获得其他常染色体的连锁信息 多基因家族，以及最近的“小卫星”探针 描述了在单个标记上检测多态标记大家族 南方污点。

Neurofibromatosis (NF) is a common human autosomal dominant condition characterized by cafe-au-lait spots, neurofibromas, and a broad range of other manifestations. Its high spontaneous mutation rate (among the highest described in man) and preliminary linkage analysis using protein polymorphisms has suggested that the responsible mutation may be at a different locus in different families. The power of linkage analysis to identify the location of a mutant gene has recently been greatly extended by the introduction of DNA polymorphisms as genetic markers, which should allow any disease gene to be mapped if appropriate families are available for study, and if a sufficient number of informative markers can be generated. NF is a highly appropriate target disorder for this approach. We propose to ascertain three or four three-generation families with NF and sufficient available family members to allow linkage analysi on single families, so that potential locus heterogeneity will not destroy any associations. Using EB virus transformed lymphocytes, we will look for evidence of linkage to GC blood group (chr. 4) and secretor (chr. 19) both of which have been suggested to show linkage to NF in some but not all families. We will also develop and study markers on chromosome 8 (where circumstantial evidence suggests the NF locus might be, and for which DNA probes are needed anyway). We will maximize the rapidity of obtaining linkage information on other autosomal chromosomes by using probes for multigene families, as well as the "minisatellite" probes recently described which detect a large family of polymorphic markers on a single Southern blot.