Pagnier J, Mears J G, Dunda-Belkhodja O, Schaefer-Rego K E, Beldjord C, Nagel R L, Labie D
Proc Natl Acad Sci U S A. 1984 Mar;81(6):1771-3. doi: 10.1073/pnas.81.6.1771.
Previous studies of the Hpa I cleavage site-sickle cell hemoglobin gene linkage in various African populations suggested that the sickle gene arose independently more than once. In the present study we have performed restriction endonuclease haplotype analysis for the beta-globin-like gene cluster from four separate geographic areas in Africa, all of which possess the sickle gene. In Benin (Central West Africa) and Algeria (Arab North Africa) all chromosomes carrying the sickle gene possess an identical haplotype as defined by 11 different polymorphic restriction endonuclease sites within the 60-kilobase region of the beta-globin-like gene cluster. In the Central African Republic (Bantu-speaking Africa) and in Senegal (Atlantic West Africa) a very large proportion of the sickle gene chromosomes were associated with a haplotype specific for each country. Thus, three different haplotypes are shown to be associated with the sickle gene in Africa, and each is present at a very high frequency in geographically separate regions. Since the three haplotypes differ from each other by at least three sites residing both 5' and 3' to a putative hot spot for recombination, it is most likely that the sickle gene arose at least three times on separate preexisting chromosomal haplotypes. This may have implications for a better understanding of the variable nature of the expression of sickle cell anemia, because clinically relevant sequences (for example, gamma-globin gene regulatory sequences responsive to anemia) might be linked polymorphically to these haplotypes.
先前对不同非洲人群中Hpa I切割位点-镰状细胞血红蛋白基因连锁的研究表明，镰状基因不止一次独立出现。在本研究中，我们对来自非洲四个不同地理区域且均携带镰状基因的β-珠蛋白样基因簇进行了限制性内切酶单倍型分析。在贝宁（中西部非洲）和阿尔及利亚（阿拉伯北非），所有携带镰状基因的染色体都具有相同的单倍型，该单倍型由β-珠蛋白样基因簇60千碱基区域内11个不同的多态性限制性内切酶位点所定义。在中非共和国（讲班图语的非洲地区）和塞内加尔（大西洋西部非洲），很大比例的镰状基因染色体与每个国家特有的单倍型相关联。因此，在非洲显示出三种不同的单倍型与镰状基因相关，并且每种单倍型在地理上相互独立的区域中都以非常高的频率出现。由于这三种单倍型在假定的重组热点的5'和3'两侧至少有三个位点彼此不同，所以镰状基因很可能在单独存在于先前的染色体单倍型上至少出现了三次。这可能对更好地理解镰状细胞贫血表达的可变性质具有启示意义，因为临床相关序列（例如，对贫血有反应的γ-珠蛋白基因调控序列）可能与这些单倍型呈多态性连锁。
