The USH1C 216G-->A mutation and the 9-repeat VNTR(t,t) allele are in complete linkage disequilibrium in the Acadian population.
Recently, mutations in USH1C were shown to be associated with Usher syndrome type IC, and a mutation (216G-->A) in exon 3 was identified in an Acadian family. In addition, a 45-bp variable number of tandem repeat (VNTR) polymorphism was found in intron 5 of USH1C. Polymerase chain reaction amplification of the VNTR region and restriction enzyme analysis of exon 3 of USH1C showed that, of 44 Acadian patients, 43 were homozygous for both the 216G-->A mutation and nine repeats of the VNTR, with a "t" nucleotide replacing a "g" nucleotide at the 8th position of both the eighth and ninth copies of the repeat, viz., 9VNTR(t,t). The remaining Acadian patient was reported to be a compound heterozygote for 216G-->A/9VNTR(t,t) and 238-239insC, a USH1C mutation that has been found in other populations. These data demonstrate that the 9VNTR(t,t) allele is in complete linkage disequilibrium with the 216G-->A mutation in the Acadian population. Among 82 Acadian controls, one was heterozygous for 216G-->A/9VNTR(t,t). The 238-239insC mutation was not found in Acadian controls. Analysis of 340 non-Acadian normal samples showed the presence of a 9-repeat VNTR allele in one Hispanic sample. This individual had neither the 216G-->A mutation nor the Acadian VNTR(t,t) structure. These results suggest that the 216G-->A mutation and the 9VNTR(t,t) allele are restricted to the Acadians and are in complete linkage disequilibrium.
Savas
Sevtap
S
Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA 70112, USA.
Frischhertz
Ben
B
Pelias
Mary Z
MZ
Batzer
Mark A
MA
Deininger
Prescott L
PL
Keats
Bronya B
BB
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005006:Ethnicity / Q000235:genetics; D006311:Hearing Disorders / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008145:Louisiana; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012162:Retinal Degeneration / Q000235:genetics; D013577:Syndrome
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C118970:USH1C protein, human