TY - JOUR
T1 - FOXP2
T2 - Novel exons, splice variants, and CAG repeat length stability
AU - Bruce, Heather A.
AU - Margolis, Russell L.
N1 - Funding Information:
Acknowledgements We thank John Kleiderlein, John Hwang, Daniel Gorelick-Feldman, and Kirsten Bottoms for technical assistance, and gratefully acknowledge the guidance and support of Christopher A. Ross, Susan E. Holmes, Doda Rudnicki, Logan Bruce, and Eric Johnson. This work was supported by a Johns Hopkins University Provost’s Research Award to H.A.B., and NIH grants NS38054, MH02175, and NS16375.
PY - 2002/8
Y1 - 2002/8
N2 - FOXP2 is a transcription factor containing a polyglutamine tract, a zinc-finger motif, and a forkhead DNA-binding domain. The FOXP2 gene is located in 7q31. A misense mutation in the forkhead domain (exon 14) and a balanced reciprocal translocation t(5;7)(q22;31.2) with a breakpoint between exons 3b and 4 have recently been associated with a speech and language disorder (SPCH1). The role of FOXP2 in this neurodevelopmental disorder suggests that mutations in FOXP2 could cause other neuropsychiatric disorders. To begin investigation of this possibility, we examined the genomic structure and CAG/CAA repeat region of FOXP2. We detected little polymorphism and no expansions in the FOXP2 CAG/CAA repeat in 142 individuals with progressive movement disorders. We found evidence of alternate splice variants and six previously undetected exons: three 5′ untranslated exons (s1, s2, s3), two additional untranslated exons (2a and 2b) between exons 2 and 3, a translated exon (4a) between exons 4 and 5, and a longer version of exon 10 (10+) that contains an alternate stop codon and produces a truncated protein (FOXP2-S). Our results suggest that FOXP2 spans at least 603 kb of genomic DNA, more than twice the previously defined region, and provide evidence of a promoter region flanking exons s1. This demonstration of additional FOXP2 exons and splice variants should facilitate understanding of FOXP2 function and the search for additional FOXP2 mutations.
AB - FOXP2 is a transcription factor containing a polyglutamine tract, a zinc-finger motif, and a forkhead DNA-binding domain. The FOXP2 gene is located in 7q31. A misense mutation in the forkhead domain (exon 14) and a balanced reciprocal translocation t(5;7)(q22;31.2) with a breakpoint between exons 3b and 4 have recently been associated with a speech and language disorder (SPCH1). The role of FOXP2 in this neurodevelopmental disorder suggests that mutations in FOXP2 could cause other neuropsychiatric disorders. To begin investigation of this possibility, we examined the genomic structure and CAG/CAA repeat region of FOXP2. We detected little polymorphism and no expansions in the FOXP2 CAG/CAA repeat in 142 individuals with progressive movement disorders. We found evidence of alternate splice variants and six previously undetected exons: three 5′ untranslated exons (s1, s2, s3), two additional untranslated exons (2a and 2b) between exons 2 and 3, a translated exon (4a) between exons 4 and 5, and a longer version of exon 10 (10+) that contains an alternate stop codon and produces a truncated protein (FOXP2-S). Our results suggest that FOXP2 spans at least 603 kb of genomic DNA, more than twice the previously defined region, and provide evidence of a promoter region flanking exons s1. This demonstration of additional FOXP2 exons and splice variants should facilitate understanding of FOXP2 function and the search for additional FOXP2 mutations.
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U2 - 10.1007/s00439-002-0768-5
DO - 10.1007/s00439-002-0768-5
M3 - Article
C2 - 12189486
AN - SCOPUS:0036705625
SN - 0340-6717
VL - 111
SP - 136
EP - 144
JO - Human genetics
JF - Human genetics
IS - 2
ER -