Unexpected findings in TALS/MOPD1 : an illustration of homozygosity mapping by genomic control

Author: A. Leutenneger
Submitted: Friday 6th of July 2012 10:11:31 AM
Submitted by: egf
Language: English
Content type: Learning resource
Educational levels: qc2, qc3

Abstract

Taybi-Linder syndrome/MOPD1 [OMIM 210710] is a rare recessive disorder characterized by brain and bone malformations and unexplained postnatal death. Only a small sample of patients without well-characterized consanguinity was available for study. Because genealogical information was unreliable, the individuals’ inbreeding coefficients were inferred from genome scan data (FEstim, Leutenegger et al, 2003). Using these genomic estimates to perform homozygosity mapping, the disease locus was successfully mapped to chromosome 2q (Leutenegger al al, 2006). Subsequently, targeted next generation sequencing (NGS) of the complete candidate region allowed us to identify point mutations in the U4atac small nuclear RNA component of the minor spliceosome (Edery et al, 2011). The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for protein translation. References : Edery P, Marcaillou C, Sahbatou M, Labalme A, Chastang J, Touraine R, Tubacher E, Senni F, Bober MB, Nampoothiri S, Jouk PS, Steichen E, Berland S, Toutain A, Wise CA, Sanlaville D, Rousseau F, Clerget-Darpoux F, Leutenegger AL. Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA. Science. 2011 Apr 8;332(6026):240-3. Leutenegger AL, Labalme A, Genin E, Toutain A, Steichen E, Clerget-Darpoux F, Edery P. Using genomic inbreeding coefficient estimates for homozygosity mapping of rare recessive traits: application to Taybi-Linder syndrome. Am J Hum Genet. 2006 Jul;79(1):62-6. Leutenegger AL, Prum B, Génin E, Verny C, Lemainque A, Clerget-Darpoux F, Thompson EA. Estimation of the inbreeding coefficient through use of genomic data. Am J Hum Genet. 2003 Sep;73(3):516-23.

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abstract leutenegger_tals_bologna2012x_v2_5222.pdf

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A. Leutenneger. Unexpected findings in TALS/MOPD1 : an illustration of homozygosity mapping by genomic control. EUROGENE portal. July 2012. online: http://eurogene.open.ac.uk/content/unexpected-findings-talsmopd1-illustration-homozygosity-mapping-genomic-control

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