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疾病 其特征在于黑素斑、神经纤维瘤和广泛的 其他表现。 它的高自发突变率（在 最高描述的人）和初步连锁分析使用蛋白质 多态性表明，负责的突变可能是在一个 不同家庭的基因座不同。 连锁分析的力量，以确定突变基因的位置， 最近通过引入DNA多态性， 遗传标记，这应该允许任何疾病基因被映射，如果 适当的家庭可供研究，如果有足够数量的 可以产生信息标记。 NF是一个非常合适的目标 这种做法的弊端。 我们建议确定三个或四个三代家庭与NF， 足够的可用家族成员，以允许对单个 家庭，因此，潜在的基因座异质性不会破坏任何 协会. 使用EB病毒转化的淋巴细胞，我们将寻找 与GC血型（chr. 4）和分泌型（chr. 19）相关的证据， 其中一些已被认为与NF连锁，但不是全部 家庭 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NF基因座可能是， 无论如何都需要探针）。 我们将最大限度地快速获取 通过使用探针在其他常染色体上的连锁信息 多基因家族，以及最近的“小卫星”探针 所描述的方法检测单个基因组上的大家族多态性标记， Southern blot

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.