Beckers M C, Ernst E, Diez E, Morissette C, Gervais F, Hunter K, Housman D, Yoshida S, Skamene E, Gros P
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Genomics. 1997 Feb 1;39(3):254-63. doi: 10.1006/geno.1996.4489.
Natural resistance of inbred mouse strains to infection with Legionella pneumophila is controlled by the expression of a single dominant gene on chromosome 13, designated Lgn1. The genetic difference at Lgn1 is phenotypically expressed as the presence or absence of intracellular replication of L. pneumophila in host macrophages. In our effort to identify the Lgn1 gene by positional cloning, we have generated a high-resolution linkage map of the Lgn1 chromosomal region. For this, we have carried out extensive segregation analysis in a total of 1270 (A/J x C57BL/6J) x A/J informative backcross mice segregating the resistance allele of C57BL/6J and the susceptibility allele of A/J. Additional segregation analyses were carried out in three preexisting panels of C57BL/6J x Mus spretus interspecific backcross mice. A total of 39 DNA markers were mapped within an interval of approximately 30 cM overlapping the Lgn1 region. Combined pedigree analyses for the 5.4-cM segment overlapping Lgn1 indicated the locus order and the interlocus distances (in cM): D13Mit128-(1.4)-D13Mit194-(0.1)-D13Mit147-(0.9)-D13 Mit36-(0.9)-D13Mit146-(0.2)-Lgn1/D13Mit37-(1.0)- D13Mit70. Additional genetic linkage studies of markers not informative in the A/J x C57BL/6J cross positioned D13Mit30, -72, -195, and -203, D13Gor4, D13Hun35, and Mtap5 in the immediate vicinity of the Lgn1 locus. The marker density and resolution of this genetic linkage map should allow the construction of a physical map of the region and the isolation of YAC clones overlapping the gene.
近交系小鼠对嗜肺军团菌感染的天然抗性由位于13号染色体上的一个显性基因Lgn1的表达所控制。Lgn1基因的遗传差异在表型上表现为宿主巨噬细胞中嗜肺军团菌是否进行细胞内复制。为了通过定位克隆来鉴定Lgn1基因，我们构建了Lgn1染色体区域的高分辨率连锁图谱。为此，我们在总共1270只（A/J×C57BL/6J）×A/J信息性回交小鼠中进行了广泛的分离分析，这些小鼠分离出C57BL/6J的抗性等位基因和A/J的易感等位基因。另外，在三个现有的C57BL/6J×小家鼠种间回交小鼠群体中进行了分离分析。总共39个DNA标记被定位在与Lgn1区域重叠的大约30厘摩区间内。对与Lgn1重叠的5.4厘摩片段进行的联合系谱分析表明了基因座顺序和基因座间距离（以厘摩计）：D13Mit128-（1.4）-D13Mit194-（0.1）-D13Mit147-（0.9）-D13 Mit36-（0.9）-D13Mit146-（0.2）-Lgn1/D13Mit37-（1.0）- D13Mit70。对在A/J×C57BL/6J杂交中无信息的标记进行的额外遗传连锁研究将D13Mit30、-72、-195和-203、D13Gor4、D13Hun35和Mtap5定位在Lgn1基因座的紧邻区域。这个遗传连锁图谱的标记密度和分辨率应该能够构建该区域的物理图谱并分离出与该基因重叠的酵母人工染色体（YAC）克隆。
