Assessment of complement C4 gene copy number using the paralog ratio test

Human Mutation

Volumn 31, Issue 7, 2010, Pages 866-874

  Fernando, Michelle M A ^a   Boteva, Lora ^a   Morris, David L ^a   Zhou, Bi ^b   Wu, Yee Ling ^b   Lokki, Marja Liisa ^c   Yu, Chack Yung ^b   Rioux, John D ^d,e   Hollox, Edward J ^f   Vyse, Timothy J ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b NATIONWIDE CHILDREN S HOSPITAL   (United States)

^c UNIVERSITY OF HELSINKI   (Finland)

^d MONTREAL HEART INSTITUTE   (Canada)

^e UNIVERSITÉ DE MONTRÉAL   (Canada)

^f UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

CNV; Complement C4; Lupus; Paralog ratio test

Indexed keywords

BETA DEFENSIN; RESTRICTION ENDONUCLEASE; COMPLEMENT COMPONENT C4;

ALLELE; ARTICLE; COMPLEMENT C4 GENE; CONTROLLED STUDY; COPY NUMBER VARIATION; CORRELATION ANALYSIS; FCGR3 GENE; GENE; GENE LOCUS; GENE STRUCTURE; GENETIC ANALYSIS; GENOTYPE; PARALOG RATIO TEST; POPULATION RESEARCH; PRIORITY JOURNAL; RESTRICTION ENZYME DIGEST VARIANT RATIO DETERMINATION; SOUTHERN BLOTTING; CAUCASIAN; GENE DOSAGE; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETICS; HAPLOTYPE; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; MUTATION; PROCEDURES; REPRODUCIBILITY; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS;

ALLELES; COMPLEMENT C4; EUROPEAN CONTINENTAL ANCESTRY GROUP; GENE DOSAGE; GENE FREQUENCY; GENETIC ASSOCIATION STUDIES; GENOTYPE; HAPLOTYPES; HUMANS; LINKAGE DISEQUILIBRIUM; LUPUS ERYTHEMATOSUS, SYSTEMIC; MAJOR HISTOCOMPATIBILITY COMPLEX; MUTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; REPRODUCIBILITY OF RESULTS;

EID: 77954109371     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.21259     Document Type: Article

References (52)

1. Aldred PM, Hollox EJ, Armour JA. 2005. Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3. Hum Mol Genet 14:2045-2052.
2. Arason GJ, Kramer J, Blasko B, Kolka R, Thorbjornsdottir P, Einarsdottir K, Sigfusdottir A, Sigurdarson ST, Sigurdsson G, Ronai Z, Prohászka Z, Sasvári-Székely M, Bödvarsson S, Thorgeirsson G, Füst G. 2007. Smoking and a complement gene polymorphism interact in promoting cardiovascular disease morbidity and mortality. Clin Exp Immunol 149:132-138.
3. Armour JA, Palla R, Zeeuwen PL, den Heijer M, Schalkwijk J, Hollox EJ. 2007. Accurate, high-throughput typing of copy number variation using paralogue ratios from dispersed repeats. Nucleic Acids Res 35:e19.
4. Awdeh ZL, Raum D, Yunis EJ, Alper CA. 1983. Extended HLA/complement allele haplotypes: evidence for T/t-like complex in man. Proc Natl Acad Sci USA 80:259-263.
5. Barba G, Rittner C, Schneider PM. 1993. Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression. J Clin Invest 91:1681-1686. (Pubitemid 23127373)
6. Blanchong CA, Zhou B, Rupert KL, Chung EK, Jones KN, Sotos JF, Zipf WB, Rennebohm RM, Yung Yu C. 2000. Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease. J Exp Med 191:2183-2196. (Pubitemid 30416364)
7. Briggs D, Stephens C, Vaughan R, Welsh K, Black C. 1993. A molecular and serologic analysis of the major histocompatibility complex and complement component C4 in systemic sclerosis. Arthritis Rheum 36:943-954. (Pubitemid 23201109)
8. Carroll MC, Palsdottir A, Belt KT, Porter RR. 1985. Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region. EMBO J 4:2547-2552.
9. Christiansen FT, Dawkins RL, Uko G, McCluskey J, Kay PH, Zilko PJ. 1983. Complement allotyping in SLE: association with C4A null. Aust N Z J Med 13:483-488. (Pubitemid 14175164)
10. Christiansen FT, Zhang WJ, Griffiths M, Mallal SA, Dawkins RL. 1991. Major histocompatibility complex (MHC) complement deficiency, ancestral haplotypes and systemic lupus erythematosus (SLE): C4 deficiency explains some but not all of the influence of the MHC. J Rheumatol 18:1350-1358.
11. Chung EK, Wu YL, Yang Y, Zhou B, Yu CY. 2005. Human complement components C4A and C4B: complex genotypes and phenotypes. In: Coligan JE, Bierer BE, Margulis DH, Shevach EM, Strober W, editors. Current protocols in immunology. Edison, NJ: John Wiley & Sons. p 13.8.1-13.8.36.
12. Chung EK, Yang Y, Rennebohm RM, Lokki ML, Higgins GC, Jones KN, Zhou B, Blanchong CA, Yu CY. 2002. Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex. Am J Hum Genet 71:823-837. (Pubitemid 135750515)
13. Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P, Fitzgerald T, Hu M, Ihm CH, Kristiansson K, Macarthur DG, Macdonald JR, Onyiah I, Pang AW, Robson S, Stirrups K, Valsesia A, Walter K, Wei J; Wellcome Trust Case Control Consortium, Tyler-Smith C, Carter NP, Lee C, Scherer SW, Hurles ME. 2009. Origins and functional impact of copy number variation in the human genome. Nature 464:704-712.
14. Dangel AW, Mendoza AR, Baker BJ, Daniel CM, Carroll MC, Wu LC, Yu CY. 1994. The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates. Immunogenetics 40:425-436.
15. Dawkins R, Leelayuwat C, Gaudieri S, Tay G, Hui J, Cattley S, Martinez P, Kulski J. 1999. Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease. Immunol Rev 167:275-304. (Pubitemid 29178988)
16. Dodds AW, Ren XD, Willis AC, Law SK. 1996. The reaction mechanism of the internal thioester in the human complement component C4. Nature 379:177-179.
17. Fielder AH, Walport MJ, Batchelor JR, Rynes RI, Black CM, Dodi IA, Hughes GR. 1983. Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. Br Med J (Clin Res Ed) 286:425-428.
18. Fischer MB, Ma M, Goerg S, Zhou X, Xia J, Finco O, Han S, Kelsoe G, Howard RG, Rothstein TL, Kremmer E, Rosen FS, Carroll MC. 1996. Regulation of the B cell response to T-dependent antigens by classical pathway complement. J Immunol 157:549-556. (Pubitemid 26231355)
19. Franciotta D, Cuccia M, Dondi E, Piccolo G, Cosi V. 2001. Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis. J Neurol Sci 190:11-16.
20. Hollox EJ, Detering JC, Dehnugara T. 2009. An integrated approach for measuring copy number variation at the FCGR3 (CD16) locus. Hum Mutat 30:477-484.
21. Hollox EJ, Huffmeier U, Zeeuwen PL, Palla R, Lascorz J, Rodijk-Olthuis D, van de Kerkhof PC, Traupe H, de Jongh G, den Heijer M, Reis A, Armour JA, Schalkwijk J. 2008. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 40:23-25.
22. Isenman DE, Young JR. 1984. The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. J Immunol 132:3019-3027.
23. Kramer J, Rajczy K, Fust G. 1989. Low incidence of null alleles of the fourth component of complement (C4) in elderly people. Immunol Lett 20:83-85. (Pubitemid 19032969)
24. Law SK, Dodds AW, Porter RR. 1984. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J 3:1819-1823.
25. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G, Lin Y, MacDonald JR, Pang AW, Shago M, Stockwell TB, Tsiamouri A, Bafna V, Bansal V, Kravitz SA, Busam DA, Beeson KY, McIntosh TC, Remington KA, Abril JF, Gill J, Borman J, Rogers YH, Frazier ME, Scherer SW, Strausberg RL, Venter JC. 2007. The diploid genome sequence of an individual human. PLoS Biol 5:e254.
26. Locke DP, Sharp AJ, McCarroll SA, McGrath SD, Newman TL, Cheng Z, Schwartz S, Albertson DG, Pinkel D, Altshuler DM, Eichler EE. 2006. Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. Am J Hum Genet 79:275-290. (Pubitemid 44141826)
27. McCarroll SA. 2008. Extending genome-wide association studies to copy-number variation. Hum Mol Genet 17:R135-R142.
28. Montgomery RA, Dietz HC. 1997. Inhibition of fibrillin 1 expression using U1 snRNA as a vehicle for the presentation of antisense targeting sequence. Hum Mol Genet 6:519-525.
29. NavesM, Hajeer AH, Teh LS, Davies EJ, Ordi-Ros J, Perez-Pemen P, Vilardel-Tarres M, Thomson W,Worthington J, Ollier WE. 1998. Complement C4B null allele status confers risk for systemic lupus erythematosus in a Spanish population. Eur J Immunogenet 25:317-320. (Pubitemid 28408297)
30. Odell D, Maciulis A, Cutler A, Warren L, McMahon WM, Coon H, Stubbs G, Henley K, Torres A. 2005. Confirmation of the association of the C4B null allelle in autism. Hum Immunol 66:140-145. (Pubitemid 40208201)
31. Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ. 2000. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 76:227-324.
32. Pickering MC, Walport MJ. 2000. Links between complement abnormalities and systemic lupus erythematosus. Rheumatology (Oxford) 39:133-141. (Pubitemid 30139345)
33. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A,Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME. 2006. Global variation in copy number in the human genome. Nature 444:444-454. (Pubitemid 44809057)
34. Rioux JD, Goyette P, Vyse TJ, Hammarstrom L, Fernando MM, Green T, De Jager PL, Foisy S, Wang J, de Bakker PI, Leslie S, McVean G, Padyukov L, Alfredsson L, Annese V, Hafler DA, Pan-Hammarström Q, Matell R, Sawcer SJ, Compston AD, Cree BA, Mirel DB, Daly MJ, Behrens TW, Klareskog L, Gregersen PK, Oksenberg JR, Hauser SL 2009. Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases. Proc Natl Acad Sci USA 106:18680-18685.
35. Rozen S, Skaletsky H. 2000. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365-386.
36. Saxena K, Kitzmiller KJ, Wu YL, Zhou B, Esack N, Hiremath L, Chung EK, Yang Y, Yu CY. 2009. Great genotypic and phenotypic diversities associated with copynumber variations of complement C4 and RP-C4-CYP21-TNX (RCCX) modules: a comparison of Asian-Indian and European American populations. Mol Immunol 46:1289-1303.
37. Seppanen M, Meri S, Notkola IL, Seppala IJ, Hiltunen-Back E, Sarvas H, Lappalainen M, Valimaa H, Palikhe A, Valtonen VV, Lokki ML. 2006a. Subtly impaired humoral immunity predisposes to frequently recurring genital herpes simplex virus type 2 infection and herpetic neuralgia. J Infect Dis 194:571-578. (Pubitemid 44297840)
38. Seppanen M, Suvilehto J, Lokki ML, Notkola IL, Jarvinen A, Jarva H, Seppala I, Tahkokallio O, Malmberg H, Meri S, Valtonen V. 2006b. Immunoglobulins and complement factor C4 in adult rhinosinusitis. Clin Exp Immunol 145:219-227.
39. Shen L, Wu LC, Sanlioglu S, Chen R, Mendoza AR, Dangel AW, Carroll MC, Zipf WB, Yu CY. 1994. Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication. J Biol Chem 269:8466-8476.
40. Stefansson Thors V, Kolka R, Sigurdardottir SL, Edvardsson VO, Arason G, Haraldsson A. 2005. Increased frequency of C4B*Q0 alleles in patients with Henoch-Schonlein purpura. Scand J Immunol 61:274-278. (Pubitemid 40462778)
41. The International HapMap Consortium. 2003. The International HapMap Project. Nature 426:789-796.
42. Traherne JA, Horton R, Roberts AN, Miretti MM, Hurles ME, Stewart CA, Ashurst JL, Atrazhev AM, Coggill P, Palmer S, Almeida J, Sims S, Wilming LG, Rogers J, de Jong PJ, Carrington M, Elliott JF, Sawcer S, Todd JA, Trowsdale J, Beck S. 2006. Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history. PLoS Genet 2:e9.
43. Vergani D, Wells L, Larcher VF, Nasaruddin BA, Davies ET, Mieli-Vergani G, Mowat AP. 1985. Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis. Lancet 2:294-298. (Pubitemid 15045129)
44. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP, Lupski JR, Chinault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Qin X, Muzny DM, Margulies M, Weinstock GM, Gibbs RA, Rothberg JM. 2008. The complete genome of an individual by massively parallel DNA sequencing. Nature 452:872-876.
45. Wu YL, Hauptmann G, Viguier M, Yu CY. 2009. Molecular basis of complete complement C4 deficiency in two North-African families with systemic lupus erythematosus. Genes Immun 10:433-445.
46. Wu YL, Yang Y, Chung EK, Zhou B, Kitzmiller KJ, Savelli SL, Nagaraja HN, Birmingham DJ, Tsao BP, Rovin BH, Hebert LA, Yu CY. 2008. Phenotypes, genotypes and disease susceptibility associated with gene copy number variations: complement C4 CNVs in European American healthy subjects and those with systemic lupus erythematosus. Cytogenet Genome Res 123:131-141.
47. Yang Y, Chung EK, Wu YL, Savelli SL, Nagaraja HN, Zhou B, Hebert M, Jones KN, Shu Y, Kitzmiller K, Blanchong CA, McBride KL, Higgins GC, Rennebohm RM, Rice RR, Hackshaw KV, Roubey RA, Grossman JM, Tsao BP, Birmingham DJ, Rovin BH, Hebert LA, Yu CY. 2007. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Genet 80:1037-1054.
48. Yang Y, Chung EK, Zhou B, Blanchong CA, Yu CY, Fust G, Kovacs M, Vatay A, Szalai C, Karadi I, Varga L. 2003. Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index. J Immunol 171:2734-2745. (Pubitemid 37025587)
49. Yang Z, Mendoza AR, Welch TR, Zipf WB, Yu CY. 1999. Modular variations of the human major histocompatibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease associations. J Biol Chem 274:12147-12156.
50. Yu CY. 1991. The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21- hydroxylase gene. J Immunol 146:1057-1066.
51. Yu CY, Belt KT, Giles CM, Campbell RD, Porter RR. 1986. Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. EMBO J 5:2873-2881.
52. Yu CY, Campbell RD. 1987. Definitive RFLPs to distinguish between the human complement C4A/C4B isotypes and the major Rodgers/Chido determinants: application to the study of C4 null alleles. Immunogenetics 25:383-390.