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A gene for Meckel syndrome maps to chromosome 11q13
J Roume1, E Genin, V Cormier-Daire
1Unité de Recherches sur les Handicaps Génétiques de lEnfant, INSERMU. 393, France.
Abstract:
Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown origin, characterized by (i) an occipital meningo-encephalocele with (ii) enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and (iii) postaxial polydactyly. A gene responsible for MKS in Finland has been mapped to chromosome 17q21-q24. Studying a subset of Middle Eastern and northern African MKS families, we have recently excluded the chromosome 17 region and have suggested a genetic heterogeneity. In the present study, we report on the mapping of a second MKS locus (MKS2) to chromosome 11q13, by homozygosity mapping in seven families that do not show linkage to chromosome 17q21-q24 (maximum LOD score 4.41 at recombination fraction .01). Most interestingly, the affected fetuses of southern Tunisian ancestry shared a particular haplotype at loci D11S911 and D11S906, suggesting that a founder effect is involved. Our observation gives support to the clinical and genetic heterogeneity of MKS.
Insights
Meckel syndrome (MKS) is a rare genetic disorder. Researchers identified a second gene locus (MKS2) on chromosome 11q13, indicating genetic heterogeneity in MKS.
Area of Science:
- Medical Genetics
- Developmental Biology
- Human Genetics
Background:
- Meckel syndrome (MKS) is a rare, lethal autosomal recessive condition.
- MKS is characterized by occipital meningo-encephalocele, enlarged kidneys with multicystic dysplasia, liver fibrosis, and postaxial polydactyly.
- Previous studies mapped a gene for MKS to chromosome 17q21-q24, but genetic heterogeneity was suspected.
Purpose of the Study:
- To identify additional genetic loci responsible for Meckel syndrome.
- To investigate the genetic heterogeneity of Meckel syndrome in families not linked to the chromosome 17 locus.
Main Methods:
- Homozygosity mapping was performed on seven MKS families.
- Linkage analysis was conducted to exclude the chromosome 17 region.
- Haplotype analysis was used to investigate potential founder effects in specific populations.
Main Results:
- A second MKS locus, designated MKS2, was mapped to chromosome 11q13.
- Linkage to chromosome 17q21-q24 was excluded in these families (maximum LOD score 4.41 at recombination fraction 0.01).
- Affected fetuses of southern Tunisian ancestry shared a specific haplotype, suggesting a founder effect.
Conclusions:
- Meckel syndrome exhibits genetic heterogeneity, with at least two distinct loci identified.
- The MKS2 locus on chromosome 11q13 is responsible for MKS in some families.
- A founder effect may contribute to the prevalence of MKS in certain populations, such as those of southern Tunisian ancestry.