title: Dating the origin of the V170M mutation causing non-type I cystinuria in Libyan Jews by linkage disequilibrium and physical mapping of the SLC7A9 gene.
abstract: Cystinuria is an autosomal recessive disorder of the transepithelial transport of amino acids, clinically manifested by the development of kidney stones. Mutations in the gene encoding rBAT (SLC3A1, on chromosome 2p16.3) are linked to type I cystinuria, while the SLC7A9 locus (19q13.1), expressing b0,+ AT protein, is involved in non-type I cystinuria, which is very common among Libyan Jews. Applying two methods for linkage disequilibrium analysis to haplotype data spanning six 19q12-q13.1 polymorphic markers, and relying on the physical distances between the markers and the recently mapped SLC7A9 (CSNU3) locus, the age of the founder missense V170M mutation causing non-type I cystinuria in Jews of Libyan ancestry is calculated to be approximately 14 to 15 generations (g) (95% confidence interval: 9-20 g) or slightly more. The estimated age dates the most recent common ancestor of the mutation-bearing chromosomes back to the time (or some decades before) Jewish families settled in Libya following their expulsion from the Iberian Peninsula. This finding makes the molecular population genetics of cystinuria understandable in the context of the Libyan Jews' history.
authors.affiliation: Human Biology and Genetics Research Unit, Department of Psychology, Catholic University of the Sacred Heart, Largo A. Gemelli 1, Milan, 20123, Italy. rcolombo@aixmiced.mi.unicatt.it
authors.forename: R
authors.initials: R
authors.lastname: Colombo
mesh_terms: D019943:Amino Acid Substitution; D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins / Q000235:genetics*; D002871:Chromosome Banding; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003555:Cystinuria / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007585:Jews / Q000235:genetics*; D008002:Libya; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009154:Mutation; D020161:Physical Chromosome Mapping; D021122:Protein Subunits
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D021122:Protein Subunits; C499489:SLC7A9 protein, human