Skip to main content
SpringerLink
Log in

Population-specific differences in gene conversion patterns between human SUZ12 and SUZ12P are indicative of the dynamic nature of interparalog gene conversion

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Nonallelic homologous gene conversion (NAHGC) resulting from interparalog recombination without crossover represents an important influence on the evolution of duplicated sequences in the human genome. In 17q11.2, different paralogous sequences mediate large NF1 deletions by nonallelic homologous recombination with crossover (NAHR). Among these paralogs are SUZ12 and its pseudogene SUZ12P which harbour the breakpoints of type-2 (1.2-Mb) NF1 deletions. Such deletions are caused predominantly by mitotic NAHR since somatic mosaicism with normal cells is evident in most patients. Investigating whether SUZ12 and SUZ12P have also been involved in NAHGC, we observed gene conversion tracts between these paralogs in both Africans (AFR) and Europeans (EUR). Since germline type-2 NF1 deletions resulting from meiotic NAHR are very rare, the vast majority of the gene conversion tracts in SUZ12 and SUZ12P are likely to have resulted from mitotic recombination during premeiotic cell divisions of germ cells. A higher number of gene conversion tracts were noted within SUZ12 and SUZ12P in AFR as compared to EUR. Further, the distinctive signature of NAHGC (a high number of SNPs per paralog and a high number of shared SNPs between paralogs), a characteristic of many actively recombining paralogs, was observed in both SUZ12 and SUZ12P but only in AFR and not in EUR. A novel polymorphic 2.3-kb deletion in SUZ12P was identified which exhibited a high allele frequency in EUR. We postulate that this interparalog structural difference, together with low allelic recombination rates, could have caused a reduction in NAHGC between SUZ12 and SUZ12P during human evolution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • 1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061–1073. doi:10.1038/nature09534

    Article  PubMed  Google Scholar 

  • 1000 Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65. doi:10.1038/nature11632

    Article  PubMed  Google Scholar 

  • Abecasis GR, Cookson WO (2000) GOLD–graphical overview of linkage disequilibrium. Bioinformatics 16:182–183. doi:10.1093/bioinformatics/16.2.182

    Article  CAS  PubMed  Google Scholar 

  • Aleshin A, Zhi D (2010) Recombination-associated sequence homogenization of neighboring Alu elements: signature of nonallelic gene conversion. Mol Biol Evol 27:2300–2311. doi:10.1093/molbev/msq116

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Andersen SL, Sekelsky J (2010) Meiotic versus mitotic recombination: two different routes for double-strand break repair: the different functions of meiotic versus mitotic DSB repair are reflected in different pathway usage and different outcomes. BioEssays 32:1058–1066. doi:10.1002/bies.201000087

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bamshad M, Wooding SP (2003) Signatures of natural selection in the human genome. Nat Rev Genet 4:99–111. doi:10.1038/nrg999

    Article  CAS  PubMed  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265. doi:10.1093/bioinformatics/bth457

    Article  CAS  PubMed  Google Scholar 

  • Benovoy D, Drouin G (2009) Ectopic gene conversions in the human genome. Genomics 93:27–32. doi:10.1016/j.ygeno.2008.09.007

    Article  CAS  PubMed  Google Scholar 

  • Bentley DR, Balasubramanian S, Swerdlow HP et al (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59. doi:10.1038/nature07517

    Google Scholar 

  • Betrán E, Rozas J, Navarro A, Barbadilla A (1997) The estimation of the number and the length distribution of gene conversion tracts from population DNA sequence data. Genetics 146:89–99

    PubMed Central  PubMed  Google Scholar 

  • Birve A, Sengupta AK, Beuchle D, Larsson J, Kennison JA, Rasmuson-Lestander A, Müller J (2001) Su(z)12, a novel Drosophila Polycomb group gene that is conserved in vertebrates and plants. Development 128:3371–3379

    CAS  PubMed  Google Scholar 

  • Bosch E, Hurles ME, Navarro A, Jobling MA (2004) Dynamics of a human interparalog gene conversion hotspot. Genome Res 14:835–844. doi:10.1101/gr.2177404

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Buhler S, Sanchez-Mazas A (2011) HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events. PLoS ONE 6:e14643. doi:10.1371/journal.pone.0014643

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Campbell MC, Tishkoff SA (2010) The evolution of human genetic and phenotypic variation in Africa. Curr Biol 20:R166–R173. doi:10.1016/j.cub.2009.11.050

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carvalho CM, Zhang F, Lupski JR (2010) Evolution in health and medicine Sackler colloquium: genomic disorders: a window into human gene and genome evolution. Proc Natl Acad Sci USA 107(Suppl 1):1765–1771. doi:10.1073/pnas.0906222107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Casola C, Zekonyte U, Phillips AD, Cooper DN, Hahn MW (2012) Interlocus gene conversion events introduce deleterious mutations into at least 1 % of human genes associated with inherited disease. Genome Res 22:429–435. doi:10.1101/gr.127738.111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cejka P, Plank JL, Bachrati CZ, Hickson ID, Kowalczykowski SC (2010) Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3. Nat Struct Mol Biol 17:1377–1382. doi:10.1038/nsmb.1919

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen JM, Cooper DN, Chuzhanova N, Férec C, Patrinos GP (2007) Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet 8:762–775. doi:10.1038/nrg2193

    Article  CAS  PubMed  Google Scholar 

  • Chuzhanova N, Chen JM, Bacolla A, Patrinos GP, Férec C, Wells RD, Cooper DN (2009) Gene conversion causing human inherited disease: evidence for involvement of non-B-DNA-forming sequences and recombination-promoting motifs in DNA breakage and repair. Hum Mutat 30:1189–1198. doi:10.1002/humu.21020

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dayani Y, Simchen G, Lichten M (2011) Meiotic recombination intermediates are resolved with minimal crossover formation during return-to-growth, an analogue of the mitotic cell cycle. PLoS Genet 7:e1002083. doi:10.1371/journal.pgen.1002083

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • De Raedt T, Stephens M, Heyns I, Brems H, Thijs D, Messiaen L, Stephens K, Lazaro C, Wimmer K, Kehrer-Sawatzki H, Vidaud D, Kluwe L, Marynen P, Legius E (2006) Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion. Nat Genet 38:1419–1423. doi:10.1038/ng1920

    Article  PubMed  Google Scholar 

  • Dorschner MO, Sybert VP, Weaver M, Pletcher BA, Stephens K (2000) NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum Mol Genet 9:35–46. doi:10.1093/hmg/9.1.35

    Article  CAS  PubMed  Google Scholar 

  • Dumont BL, Eichler EE (2013) Signals of historical interlocus gene conversion in human segmental duplications. PLoS ONE 8:e75949. doi:10.1371/pone/0075949

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ezawa K, Oota S, Saitou N, SMBE Tri-National Young Investigators (2006) Proceedings of the SMBE Tri-National Young Investigators’ Workshop 2005. Genome-wide search of gene conversions in duplicated genes of mouse and rat. Mol Biol Evol 23:927–940. doi:10.1093/molbev/msj093

    Article  CAS  PubMed  Google Scholar 

  • Forbes SH, Dorschner MO, Le R, Stephens K (2004) Genomic context of paralogous recombination hotspots mediating recurrent NF1 region microdeletion. Genes Chromosomes Cancer 41:12–25. doi:10.1002/gcc.20065

    Article  CAS  PubMed  Google Scholar 

  • Fredman D, White SJ, Potter S, Eichler EE, den Dunnen JT, Brookes AJ (2004) Complex SNP-related sequence variation in segmental genome duplications. Nat Genet 36:861–866. doi:10.1038/ng1401

    Article  CAS  PubMed  Google Scholar 

  • Gibbs RA, Rogers J, Katze MG et al, Rhesus Macaque Genome Sequencing and Analysis Consortium (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222–234. doi:10.1126/science.1139247

    Google Scholar 

  • Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Z, Gusic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PL, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S (2010) A draft sequence of the Neandertal genome. Science 328:710–722. doi:10.1126/science.1188021

    Article  CAS  PubMed  Google Scholar 

  • Hallast P, Nagirnaja L, Margus T, Laan M (2005) Segmental duplications and gene conversion: human luteinizing hormone/chorionic gonadotropin beta gene cluster. Genome Res 15:1535–1546. doi:10.1101/gr.4270505

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hallast P, Balaresque P, Bowden GR, Ballereau S, Jobling MA (2013) Recombination dynamics of a human Y-chromosomal palindrome: rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions. PLoS Genet 9:e1003666. doi:10.1371/journal.pgen.1003666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Han LL, Keller MP, Navidi W, Chance PF, Arnheim N (2000) Unequal exchange at the Charcot-Marie-Tooth disease type 1A recombination hot-spot is not elevated above the genome average rate. Hum Mol Genet 9:1881–1889. doi:10.1093/hmg/9.12.1881

    Article  CAS  PubMed  Google Scholar 

  • Hastings PJ (2010) Mechanisms of ectopic gene conversion. Genes 1:427–439. doi:10.3390/genes1030427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • He F, Wu DD, Kong QP, Zhang YP (2008) Intriguing balancing selection on the intron 5 region of LMBR1 in human population. PLoS ONE 3:e2948. doi:10.1371/journal.pone.0002948

    Article  PubMed Central  PubMed  Google Scholar 

  • Hoffmann FG, Opazo JC, Storz JF (2008) Rapid rates of lineage-specific gene duplication and deletion in the alpha-globin gene family. Mol Biol Evol 25:591–602. doi:10.1093/molbev/msn004

    Article  CAS  PubMed  Google Scholar 

  • Hurles ME (2001) Gene conversion homogenizes the CMT1A paralogous repeats. BMC Genom 2:11. doi:10.1186/1471-2164-2-11

    Article  CAS  Google Scholar 

  • Hurles ME, Willey D, Matthews L, Hussain SS (2004) Origins of chromosomal rearrangement hotspots in the human genome: evidence from the AZFa deletion hotspots. Genome Biol 5:R55. doi:10.1186/gb-2004-5-8-r55

    Article  PubMed Central  PubMed  Google Scholar 

  • Huson SM, Compston DA, Harper PS (1989) A genetic study of von Recklinghausen neurofibromatosis in south east Wales. II. Guidelines for genetic counselling. J Med Genet 26:712–721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jackson MS, Oliver K, Loveland J, Humphray S, Dunham I, Rocchi M, Viggiano L, Park JP, Hurles ME, Santibanez-Koref M (2005) Evidence for widespread reticulate evolution within human duplicons. Am J Hum Genet 77:824–840. doi:10.1086/497704

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jeffreys AJ, May CA (2004) Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nat Genet 36:151–156. doi:10.1038/ng1287

    Article  CAS  PubMed  Google Scholar 

  • Jeffreys AJ, Neumann R (2005) Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. Hum Mol Genet 14:2277–2287. doi:10.1093/hmg/ddi232

    Article  CAS  PubMed  Google Scholar 

  • Jenne DE, Tinschert S, Reimann H, Lasinger W, Thiel G, Hameister H, Kehrer-Sawatzki H (2001) Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. Am J Hum Genet 69:516–527. doi:10.1086/323043

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kehrer-Sawatzki H, Cooper DN (2012) NF1 microdeletions and their underlying mutational mechanisms. Chap. 14 in “Neurofibromatosis Type 1: Molecular and Cellular Biology”. In: Upadhyaya M, Cooper DN (eds), Springer, Heidelberg, pp 187–211

  • Kehrer-Sawatzki H, Kluwe L, Sandig C, Kohn M, Wimmer K, Krammer U, Peyrl A, Jenne DE, Hansmann I, Mautner VF (2004) High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene. Am J Hum Genet 75:410–423. doi:10.1086/423624

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, Hansen N, Teague B, Alkan C, Antonacci F, Haugen E, Zerr T, Yamada NA, Tsang P, Newman TL, Tüzün E, Cheng Z, Ebling HM, Tusneem N, David R, Gillett W, Phelps KA, Weaver M, Saranga D, Brand A, Tao W, Gustafson E, McKernan K, Chen L, Malig M, Smith JD, Korn JM, McCarroll SA, Altshuler DA, Peiffer DA, Dorschner M, Stamatoyannopoulos J, Schwartz D, Nickerson DA, Mullikin JC, Wilson RK, Bruhn L, Olson MV, Kaul R, Smith DR, Eichler EE (2008) Mapping and sequencing of structural variation from eight human genomes. Nature 453:56–64. doi:10.1038/nature06862

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kluwe L, Siebert R, Gesk S, Friedrich RE, Tinschert S, Kehrer-Sawatzki H, Mautner VF (2004) Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1 gene. Hum Mutat 23:111–116. doi:10.1002/humu.10299

    Article  CAS  PubMed  Google Scholar 

  • Kurotaki N, Stankiewicz P, Wakui K, Niikawa N, Lupski JR (2005) Sotos syndrome common deletion is mediated by directly oriented subunits within inverted Sos-REP low-copy repeats. Hum Mol Genet 14:535–542. doi:10.1093/hmg/ddi050

    Article  CAS  PubMed  Google Scholar 

  • Laval G, Patin E, Barreiro LB, Quintana-Murci L (2010) Formulating a historical and demographic model of recent human evolution based on resequencing data from noncoding regions. PLoS ONE 5:e10284. doi:10.1371/journal.pone.0010284

    Article  PubMed Central  PubMed  Google Scholar 

  • Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, Ramachandran S, Cann HM, Barsh GS, Feldman M, Cavalli-Sforza LL, Myers RM (2008) Worldwide human relationships inferred from genome-wide patterns of variation. Science 319:1100–1104. doi:10.1126/science.1153717

    Article  CAS  PubMed  Google Scholar 

  • Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451–1452. doi:10.1093/bioinformatics/btp187

    Article  CAS  PubMed  Google Scholar 

  • Lindsay SJ, Khajavi M, Lupski JR, Hurles ME (2006) A chromosomal rearrangement hotspot can be identified from population genetic variation and is coincident with a hotspot for allelic recombination. Am J Hum Genet 79:890–902. doi:10.1086/508709

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu P, Lacaria M, Zhang F, Withers M, Hastings PJ, Lupski JR (2011) Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-over. Am J Hum Genet 89:580–588. doi:10.1016/j.ajhg.2011.09.009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lohmueller KE, Indap AR, Schmidt S, Boyko AR, Hernandez RD, Hubisz MJ, Sninsky JJ, White TJ, Sunyaev SR, Nielsen R, Clark AG, Bustamante CD (2008) Proportionally more deleterious genetic variation in European than in African populations. Nature 451:994–997. doi:10.1038/nature06611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lopes J, Tardieu S, Silander K, Blair I, Vandenberghe A, Palau F, Ruberg M, Brice A, LeGuern E (1999) Homologous DNA exchanges in humans can be explained by the yeast double-strand break repair model: a study of 17p11.2 rearrangements associated with CMT1A and HNPP. Hum Mol Genet 8:2285–2292. doi:10.1093/hmg/8.12.2285

    Article  CAS  PubMed  Google Scholar 

  • López-Correa C, Dorschner M, Brems H, Lázaro C, Clementi M, Upadhyaya M, Dooijes D, Moog U, Kehrer-Sawatzki H, Rutkowski JL, Fryns JP, Marynen P, Stephens K, Legius E (2001) Recombination hotspot in NF1 microdeletion patients. Hum Mol Genet 10:1387–1392. doi:10.1093/hmg/10.13.1387

    Article  PubMed  Google Scholar 

  • Lupski JR (2004) Hotspots of homologous recombination in the human genome: not all homologous sequences are equal. Genome Biol 5:242. doi:10.1186/gb-2004-5-10-242

    Article  PubMed Central  PubMed  Google Scholar 

  • Massey JR (1951) The Kolmogorov–Smirnov Test for goodness of fit. J Am Stat Assoc 253:68–78. doi:10.1080/01621459.1951.10500769

    Article  Google Scholar 

  • Mautner VF, Kluwe L, Friedrich RE, Roehl AC, Bammert S, Högel J, Spöri H, Cooper DN, Kehrer-Sawatzki H (2010) Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. J Med Genet 47:623–630. doi:10.1136/jmg.2009.075937

    Article  CAS  PubMed  Google Scholar 

  • Messiaen L, Vogt J, Bengesser K, Fu C, Mikhail F, Serra E, Garcia-Linares C, Cooper DN, Lazaro C, Kehrer-Sawatzki H (2011) Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1). Hum Mutat 32:213–219. doi:10.1002/humu.21418

    Article  CAS  PubMed  Google Scholar 

  • Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prüfer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andrés AM, Eichler EE, Slatkin M, Reich D, Kelso J, Pääbo S (2012) A high-coverage genome sequence from an archaic Denisovan individual. Science 338:222–226. doi:10.1126/science.1224344

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Neuwirth EA, Honma M, Grosovsky AJ (2007) Interchromosomal crossover in human cells is associated with long gene conversion tracts. Mol Cell Biol 27:5261–5274. doi:10.1128/MCB.01852-06

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nuttle X, Huddleston J, O’Roak BJ, Antonacci F, Fichera M, Romano C, Shendure J, Eichler EE (2013) Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions. Nat Methods 10:903–909. doi:10.1038/nmeth.2572

    Article  CAS  PubMed  Google Scholar 

  • Ogorelkova M, Navarro A, Vivarelli F, Ramirez-Soriano A, Estivill X (2009) Positive selection and gene conversion drive the evolution of a brain-expressed snoRNAs cluster. Mol Biol Evol 26:2563–2571. doi:10.1093/molbev/msp173

    Article  CAS  PubMed  Google Scholar 

  • Padhukasahasram B, Rannala B (2013) Meiotic gene-conversion rate and tract length variation in the human genome. Eur J Hum Genet. doi:10.1038/ejhg.2013.30 [Epub ahead of print]

  • Pasmant E, Sabbagh A, Spurlock G, Laurendeau I, Grillo E, Hamel MJ, Martin L, Barbarot S, Leheup B, Rodriguez D, Lacombe D, Dollfus H, Pasquier L, Isidor B, Ferkal S, Soulier J, Sanson M, Dieux-Coeslier A, Bièche I, Parfait B, Vidaud M, Wolkenstein P, Upadhyaya M, Vidaud D, Members of the NF France Network (2010) NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat 31:E1506–E1518. doi:10.1002/humu.21271

    Article  CAS  PubMed  Google Scholar 

  • Pavlicek A, House R, Gentles AJ, Jurka J, Morrow BE (2005) Traffic of genetic information between segmental duplications flanking the typical 22q11.2 deletion in velo-cardio-facial syndrome/DiGeorge syndrome. Genome Res 15:1487–1495. doi:10.1101/gr.4281205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pei B, Sisu C, Frankish A, Howald C, Habegger L, Mu XJ, Harte R, Balasubramanian S, Tanzer A, Diekhans M, Reymond A, Hubbard TJ, Harrow J, Gerstein MB (2012) The GENCODE pseudogene resource. Genome Biol 13:R51. doi:10.1186/gb-2012-13-9-r51

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033–1038. doi:10.1038/nature09144

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reiter LT, Murakami T, Koeuth T, Gibbs RA, Lupski JR (1997) The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs. Hum Mol Genet 6:1595–1603. doi:10.1093/hmg/6.9.1595

    Article  CAS  PubMed  Google Scholar 

  • Roehl AC, Vogt J, Mussotter T, Zickler AN, Spöri H, Högel J, Chuzhanova NA, Wimmer K, Kluwe L, Mautner VF, Cooper DN, Kehrer-Sawatzki H (2010) Intrachromosomal mitotic nonallelic homologous recombination is the major molecular mechanism underlying type-2 NF1 deletions. Hum Mutat 31:1163–1173. doi:10.1002/humu.21340

    Article  CAS  PubMed  Google Scholar 

  • Roehl AC, Mussotter T, Cooper DN, Kluwe L, Wimmer K, Högel J, Zetzmann M, Vogt J, Mautner VF, Kehrer-Sawatzki H (2012) Tissue-specific differences in the proportion of mosaic large NF1 deletions are suggestive of a selective growth advantage of hematopoietic del(±) stem cells. Hum Mutat 33:541–550. doi:10.1002/humu.22013

    Article  CAS  PubMed  Google Scholar 

  • Rogers AR (1995) Genetic evidence for a Pleistocene population explosion. Evolution 49:608–615

    Article  Google Scholar 

  • Rogers AR, Harpending H (1992) Population growth makes waves in the distribution of pairwise genetic differences. Mol Biol Evol 9:552–569

    CAS  PubMed  Google Scholar 

  • Rosser ZH, Balaresque P, Jobling MA (2009) Gene conversion between the X chromosome and the male-specific region of the Y chromosome at a translocation hotspot. Am J Hum Genet 85:130–134. doi:10.1016/j.ajhg.2009.06.009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rozas J, Sánchez-DelBarrio JC, Messeguer X, Rozas R (2003) DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19:2496–2497. doi:10.1093/bioinformatics/btg359

    Article  CAS  PubMed  Google Scholar 

  • Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS, Waterston RH, Wilson RK, Page DC (2003) Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423:873–876. doi:10.1038/nature01723

    Article  CAS  PubMed  Google Scholar 

  • Sarbajna S, Denniff M, Jeffreys AJ, Neumann R, Soler Artigas M, Veselis A, May CA (2012) A major recombination hotspot in the XqYq pseudoautosomal region gives new insight into processing of human gene conversion events. Hum Mol Genet 21:2029–2038. doi:10.1093/hmg/dds019

    Article  CAS  PubMed  Google Scholar 

  • Sasaki M, Lange J, Keeney S (2010) Genome destabilization by homologous recombination in the germ line. Nat Rev Mol Cell Biol 11:182–195. doi:10.1038/nrm2849

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM (2010) Complete Khoisan and Bantu genomes from southern Africa. Nature 463:943–947. doi:10.1038/nature08795

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schwartz EK, Wright WD, Ehmsen KT, Evans JE, Stahlberg H, Heyer WD (2012) Mus81-Mms4 functions as a single heterodimer to cleave nicked intermediates in recombinational DNA repair. Mol Cell Biol 32:3065–3080. doi:10.1128/MCB.00547-12

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sedman L, Padhukasahasram B, Kelgo P, Laan M (2008) Complex signatures of locus-specific selective pressures and gene conversion on human growth hormone/chorionic somatomammotropin genes. Hum Mutat 29:1181–1193. doi:10.1002/humu.20767

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Steele DF, Morris ME, Jinks-Robertson S (1991) Allelic and ectopic interactions in recombination-defective yeast strains. Genetics 127:53–60

    CAS  PubMed Central  PubMed  Google Scholar 

  • Steinmann K, Cooper DN, Kluwe L, Chuzhanova NA, Senger C, Serra E, Lazaro C, Gilaberte M, Wimmer K, Mautner VF, Kehrer-Sawatzki H (2007) Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination. Am J Hum Genet 81:1201–1220. doi:10.1086/522089

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW (1983) The double-strand-break repair model for recombination. Cell 33:25–35. doi:10.1016/0092-8674(83)90331-8

    Article  CAS  PubMed  Google Scholar 

  • Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    CAS  PubMed Central  PubMed  Google Scholar 

  • Torres-Juan L, Rosell J, Sánchez-de-la-Torre M, Fibla J, Heine-Suñer D (2007) Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications. BMC Med Genet 8:14. doi:10.1186/1471-2350-8-14

    Article  PubMed Central  PubMed  Google Scholar 

  • Visser R, Shimokawa O, Harada N, Kinoshita A, Ohta T, Niikawa N, Matsumoto N (2005) Identification of a 3.0-kb major recombination hotspot in patients with Sotos syndrome who carry a common 1.9-Mb microdeletion. Am J Hum Genet 76:52–67. doi:10.1086/426950

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vogt J, Nguyen R, Kluwe L, Schuhmann M, Roehl AC, Mußotter T, Cooper DN, Mautner VF, Kehrer-Sawatzki H (2011) Delineation of the clinical phenotype associated with non-mosaic type-2 NF1 deletions: two case reports. J Med Case Rep 5:577. doi:10.1186/1752-1947-5-577

    Article  PubMed Central  PubMed  Google Scholar 

  • Vogt J, Mussotter T, Bengesser K, Claes K, Högel J, Chuzhanova N, Fu C, van den Ende J, Mautner VF, Cooper DN, Messiaen L, Kehrer-Sawatzki H (2012) Identification of recurrent type-2 NF1 microdeletions reveals a mitotic nonallelic homologous recombination hotspot underlying a human genomic disorder. Hum Mutat 33:1599–1609. doi:10.1002/humu.22171

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Fan HC, Behr B, Quake SR (2012) Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150:402–412. doi:10.1016/j.cell.2012.06.030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wolf A, Millar DS, Caliebe A, Horan M, Newsway V, Kumpf D, Steinmann K, Chee IS, Lee YH, Mutirangura A, Pepe G, Rickards O, Schmidtke J, Schempp W, Chuzhanova N, Kehrer-Sawatzki H, Krawczak M, Cooper DN (2009) A gene conversion hotspot in the human growth hormone (GH1) gene promoter. Hum Mutat 30:239–247. doi:10.1002/humu.20850

    Article  CAS  PubMed  Google Scholar 

  • Wu L, Hickson ID (2003) The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature 426:870–874. doi:10.1038/nature02253

    Article  CAS  PubMed  Google Scholar 

  • Zickler AM, Hampp S, Messiaen L, Bengesser K, Mussotter T, Roehl AC, Wimmer K, Mautner VF, Kluwe L, Upadhyaya M, Pasmant E, Chuzhanova N, Kestler HA, Högel J, Legius E, Claes K, Cooper DN, Kehrer-Sawatzki H (2012) Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions. Hum Mutat 33:372–383. doi:10.1002/humu.21644

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants from the Deutsche Forschungsgemeinschaft (KE 724/10-1 and KE 724/11-1) to H. K. S.

Author information

Authors and Affiliations

  1. Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Tanja Mussotter, Kathrin Bengesser, Josef Högel & Hildegard Kehrer-Sawatzki

  2. Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

    David N. Cooper

Authors
  1. Tanja Mussotter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathrin Bengesser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Josef Högel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David N. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hildegard Kehrer-Sawatzki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hildegard Kehrer-Sawatzki.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1340 kb)

Supplementary material 2 (PDF 144 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mussotter, T., Bengesser, K., Högel, J. et al. Population-specific differences in gene conversion patterns between human SUZ12 and SUZ12P are indicative of the dynamic nature of interparalog gene conversion. Hum Genet 133, 383–401 (2014). https://doi.org/10.1007/s00439-013-1410-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-013-1410-4

Keywords

Search

Navigation