An RFLP map for 2q33‐q37 from multicase mycobacterial and leishmanial disease families: no evidence for an Lsh/Ity/Bcg gene homologue influencing susceptibility to leprosy

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Abstract
The mycobacterial disease leprosy and tuberculosis (TB) and the leishmaniases are characterized by a wide spectrum of disease phenotypes, and by the fact that the majority of individuals exposed to the causative organisms Mycobacterium leprae, M. tuberculosis and Leishmania sp. become infected but do not present with clinical disease. In order to determine whether a human homologue to the murine macrophage resistance gene Lsh/Ity/Bcg influences susceptibility to human disease, multicase families for all three disease have been collected, and linkage analysis performed using a panel of markers in the region of human chromosome 2q33‐q37 known to be conserved with the Lsh/Ity/Bcg‐containing region of murine chromosome 1. Because of the paucity of available polymorphic markers/linkage information for 2q33‐q37, data from 35 multicase leprosy, TB and visceral leishmaniasis families (310 individuals) were first pooled to produce a detailed RFLP map of the region. Peak LOD scores well in excess of 3 were observed for linkage between adjacent pairs of a more proximal (2q33‐q35) set of markers CRYGP1, MAP2, FN1, TNP1, VIL1 and DES, and between adjacent pairs of a more distal (2q35‐q37) set COL6A3, D2S55 and D2S3. These peak LOD scores and the corresponding values for θ were used in the MAP92 program to generate a multiple two‐point map with gene order/map intervals (cM) of: CRYGP1‐4.65‐MAP2‐3.45‐FN1‐5.95‐TNP1‐3.41‐VIL1‐3.01‐DES‐20.14‐COL6A‐10.91‐D2S55‐3.67‐D2S3. Although local support for the placement of loci in this order was weak (LOD 2, except for DES‐COL6A3 where LOD = 6.02), the map is consistent with the gene order for those loci (Cryg, Fn‐1, Tp‐1, Vil, Des, Col6a3) previously mapped in the mouse. Data from 17 multicase leprosy families (149 individuals) were further analysed for linkage between a putative disease susceptibility locus (DSL) con