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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.
Ann Hum Genet. 1993 10; 57(4):251-71.AH

Abstract

The mycobacterial diseases 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 diseases 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 theta 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) controlling susceptibility to leprosy per se and each of the marker loci. Assuming 100% penetrance for the susceptibility allele, no positive LOD score was obtained for linkage between the DSL and any of the marker genes. Instead, the data provide convincing evidence (LOD scores < -2) that a DSL does not fall within 10-20 cM of CRYGP1, MAP2, TNP1, VIL1, DES or D2S55, or within 5-10 cM of FN1, COL6A3 or D2S3. This effectively excludes a putative DSL controlling susceptibility to leprosy per se from the entire region 2q33-q37.(

ABSTRACT

TRUNCATED AT 400 WORDS)

Authors+Show Affiliations

Department of Medicine, University of Cambridge Clinical School, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7910002

Citation

Shaw, M A., et al. "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." Annals of Human Genetics, vol. 57, no. 4, 1993, pp. 251-71.
Shaw MA, Atkinson S, Dockrell H, et al. 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. Ann Hum Genet. 1993;57(4):251-71.
Shaw, M. A., Atkinson, S., Dockrell, H., Hussain, R., Lins-Lainson, Z., Shaw, J., Ramos, F., Silveira, F., Mehdi, S. Q., & Kaukab, F. (1993). 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. Annals of Human Genetics, 57(4), 251-71.
Shaw MA, et al. 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. Ann Hum Genet. 1993;57(4):251-71. PubMed PMID: 7910002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Shaw,M A, AU - Atkinson,S, AU - Dockrell,H, AU - Hussain,R, AU - Lins-Lainson,Z, AU - Shaw,J, AU - Ramos,F, AU - Silveira,F, AU - Mehdi,S Q, AU - Kaukab,F, PY - 1993/10/1/pubmed PY - 1993/10/1/medline PY - 1993/10/1/entrez SP - 251 EP - 71 JF - Annals of human genetics JO - Ann. Hum. Genet. VL - 57 IS - 4 N2 - The mycobacterial diseases 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 diseases 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 theta 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) controlling susceptibility to leprosy per se and each of the marker loci. Assuming 100% penetrance for the susceptibility allele, no positive LOD score was obtained for linkage between the DSL and any of the marker genes. Instead, the data provide convincing evidence (LOD scores < -2) that a DSL does not fall within 10-20 cM of CRYGP1, MAP2, TNP1, VIL1, DES or D2S55, or within 5-10 cM of FN1, COL6A3 or D2S3. This effectively excludes a putative DSL controlling susceptibility to leprosy per se from the entire region 2q33-q37.(ABSTRACT TRUNCATED AT 400 WORDS) SN - 0003-4800 UR - https://www.unboundmedicine.com/medline/citation/7910002/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_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0003-4800&amp;date=1993&amp;volume=57&amp;issue=4&amp;spage=251 DB - PRIME DP - Unbound Medicine ER -