Genomewide scan for nonsyndromic cleft lip and palate in multigenerational Indian families reveals significant evidence of linkage at 13q33.1-34.

Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0002-9297 (Print) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE

Publication: 2008- : [Cambridge, MA] : Cell Press
Original Publication: Baltimore, American Society of Human Genetics.

Genetic Linkage*; Chromosomes, Human, Pair 13/*genetics ; Cleft Lip/*genetics ; Cleft Palate/*genetics; Genome, Human ; Haplotypes ; Humans ; India ; Pedigree ; Physical Chromosome Mapping

Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used approximately 10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (alpha =100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of approximately 20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families.

Hum Mol Genet. 2004 Mar 15;13(6):577-88. (PMID: 14734624)
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R73-81. (PMID: 14722155)
Hum Hered. 2003;56(4):200-11. (PMID: 15031621)
Am J Hum Genet. 1993 May;52(5):907-14. (PMID: 8488840)
Genomics. 1993 Sep;17(3):549-55. (PMID: 8244369)
Am J Med Genet. 1994 Sep 1;52(3):315-8. (PMID: 7528972)
Clin Genet. 1994 Sep;46(3):255-6. (PMID: 7820940)
Hum Genet. 1995 Mar;95(3):342-6. (PMID: 7868130)
Am J Hum Genet. 1995 Aug;57(2):257-72. (PMID: 7668251)
Nat Genet. 1995 Oct;11(2):213-5. (PMID: 7550354)
Am J Med Genet. 1995 Jul 31;58(1):50-3. (PMID: 7573156)
Am J Hum Genet. 1996 May;58(5):923-32. (PMID: 8651276)
Hum Genet. 1997 Jan;99(1):22-6. (PMID: 9003487)
Am J Hum Genet. 1998 Jul;63(1):259-66. (PMID: 9634505)
N Engl J Med. 2004 Aug 19;351(8):769-80. (PMID: 15317890)
Genet Med. 2004 May-Jun;6(3):117-25. (PMID: 15354328)
Am J Med Genet A. 2004 Oct 15;130A(3):265-71. (PMID: 15378549)
Hum Genet. 2000 Mar;106(3):345-50. (PMID: 10798365)
Rev Med Chil. 1999 Oct;127(10):1189-98. (PMID: 10835735)
Am J Med Genet. 2001 Jan 15;98(2):145-7. (PMID: 11223850)
Nat Genet. 2001 Oct;29(2):141-2. (PMID: 11559849)
Eur J Obstet Gynecol Reprod Biol. 2001 Nov;99(1):19-24. (PMID: 11604181)
Am J Med Genet. 2001 Nov 15;104(1):86-92. (PMID: 11746036)
Nat Genet. 2002 Jan;30(1):97-101. (PMID: 11731797)
Am J Hum Genet. 2004 Dec;75(6):1106-12. (PMID: 15492927)
Am J Dis Child. 1974 Aug;128(2):217-20. (PMID: 4855263)
Am J Dis Child. 1974 Aug;128(2):221-2. (PMID: 4855264)
Humangenetik. 1974;22(4):287-98. (PMID: 4139096)
Hum Genet. 1976 Apr 15;32(1):1-12. (PMID: 1262020)
Clin Genet. 1976 Jun;9(6):593-602. (PMID: 1277571)
Hum Genet. 1976 Aug 30;33(3):213-22. (PMID: 964983)
Cleft Palate J. 1977 Jul;14(3):244-8. (PMID: 267527)
Hum Genet. 1978 Dec 29;45(3):345-50. (PMID: 738734)
Clin Genet. 1979 Apr;15(4):332-45. (PMID: 436330)
Hum Genet. 1979 Nov 1;52(1):91-9. (PMID: 527979)
Am J Med Genet. 1983 Sep;16(1):15-22. (PMID: 6638065)
Afr J Med Med Sci. 1983 Jun;12(2):81-9. (PMID: 6322555)
Hum Genet. 1984;67(1):86-93. (PMID: 6745930)
Biometrics. 1986 Jun;42(2):393-9. (PMID: 3741977)
Nature. 1987 Mar 5-11;326(6108):91-2. (PMID: 2881212)
Clin Genet. 1987 Aug;32(2):129-32. (PMID: 2888553)
Am J Hum Genet. 1989 Sep;45(3):348-53. (PMID: 2570526)
Am J Hum Genet. 1992 May;50(5):1129-36. (PMID: 1570839)
J Craniofac Genet Dev Biol. 1991 Oct-Dec;11(4):372-6. (PMID: 1687471)
Genomics. 1998 Jun 15;50(3):299-305. (PMID: 9676424)
Genomics. 1998 Jul 15;51(2):177-81. (PMID: 9722939)
Am J Hum Genet. 1999 Aug;65(2):387-96. (PMID: 10417281)
Am J Hum Genet. 2005 Jan;76(1):180-3. (PMID: 15558496)
J Indian Soc Pedod Prev Dent. 2005 Jun;23(2):80-2. (PMID: 16012210)
Am J Med Genet A. 2005 Sep 1;137A(3):259-62. (PMID: 16096995)
J Med Genet. 2005 Oct;42(10):780-6. (PMID: 16199551)
PLoS Genet. 2005 Dec;1(6):e64. (PMID: 16327884)
Genomics. 1998 Dec 1;54(2):231-40. (PMID: 9828125)
Ultrasound Obstet Gynecol. 2001 Nov;18(5):422-31. (PMID: 11844159)
Cleft Palate Craniofac J. 2002 Mar;39(2):149-56. (PMID: 11879070)
Clin Genet. 2002 Apr;61(4):248-56. (PMID: 12030886)
Am J Hum Genet. 2002 Aug;71(2):349-64. (PMID: 12087515)
Nature. 2002 Aug 1;418(6897):544-8. (PMID: 12110843)
Am J Hum Genet. 2002 Oct;71(4):992-5. (PMID: 12387273)
Fetal Diagn Ther. 2002 Nov-Dec;17(6):347-51. (PMID: 12393964)
Nat Genet. 2003 Mar;33(3):382-7. (PMID: 12590262)
J Med Genet. 2003 Jun;40(6):399-407. (PMID: 12807959)
Am J Med Genet A. 2003 Dec 1;123A(2):140-7. (PMID: 14598337)
Am J Med Genet A. 2004 Feb 15;125A(1):17-22. (PMID: 14755461)
Am J Med Genet A. 2004 Feb 15;125A(1):23-7. (PMID: 14755462)
Am J Med Genet A. 2004 Feb 15;125A(1):28-37. (PMID: 14755463)
Am J Med Genet A. 2004 Mar 1;125A(2):135-44. (PMID: 14981713)

Date Created: 20060816 Date Completed: 20061019 Latest Revision: 20200824

20221213

PMC1559556

10.1086/507487

16909398