The Y chromosome has recently been suggested to have an association with prostate cancer risk in human populations. Since this chromosome is haploid and lacks recombination over most of its length, haplotypes constructed from binary markers throughout the chromosome can be used for association studies. To assess the possible Y-chromosomal contribution to prostate cancer risk, we have therefore analyzed 14 Y-chromosomal binary markers in 106 prostate cancer cases and 110 controls from the Korean population. In contrast to previous findings in the Japanese population, no statistically significant difference in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that the previously reported associations between Y-chromosomal lineages and a predisposition to, or protection against, prostate cancer might be explained by statistical fluctuations, or by genetic effects that are seen only in some environments.
Citation: Kim W, Yoo T-K, Kim S-J, Shin D-J, Tyler-Smith C, Jin H-J, et al. (2007) Lack of Association between Y-Chromosomal Haplogroups and Prostate Cancer in the Korean Population. PLoS ONE 2(1): e172. https://doi.org/10.1371/journal.pone.0000172
Academic Editor: Mikhail Blagosklonny, Ordway Research Institute, Inc., United States of America
Received: November 7, 2006; Accepted: December 21, 2006; Published: January 24, 2007
Copyright: © 2007 Kim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: WK is supported by a grant from the Korean Science and Engineering Foundation (KOSEF R01-2005-000-10534-0), Republic of Korea. CTS is supported by The Wellcome Trust.
Competing interests: The authors have declared that no competing interests exist.
Prostate cancer is one of the most common male-specific cancers, but its incidence varies considerably between populations, with the chance of developing this cancer being highest in Western countries and lowest in Asian countries. Recent surveys suggest that both genetic alterations and dietary factors may be linked to prostate cancer –, although the etiology of this disease remains unclear in the majority of cases.
There is increasing evidence for a Y-chromosomal role in malignancy and male-specific cancer progression. Y-chromosomal mutations are associated with prostate cancer, since the loss of this chromosome is the most common chromosomal aberration observed in prostate cancer tissue , . Many genes or loci on the Y chromosome may contribute not only to male germ cell development and maintenance, but also to the molecular mechanisms of development and progression of prostate cancer –. For instance, SRY, the sex determining gene on the Y chromosome, is down-regulated in this cancer and is a negative regulator of the androgen receptor . The SRY gene thus seems to be candidate for involvement in the oncogenesis of prostate cancer .
The Y chromosome has special genetic features that include an absence of recombination over most of its length and haploid status. The DNA sequence of the non-recombining region of the Y chromosome therefore contains a record only of the mutational events that occurred in the past. As a consequence, haplotypes constructed from Y-chromosomal alleles have been successfully used to study paternal lineages – and to differentiate human population groups –. In addition, any mutation predisposing to, or protecting against, prostate cancer will lie on the well-established phylogeny, so that the binary markers that define the lineages can also be used for association studies. In addition, since Y-chromosomal lineages (i.e. haplogroups) are highly stratified among human populations, such a haplogroup-specific association is likely to be population-specific as well.
Interestingly, recent studies have suggested that certain Y-chromosomal lineages were associated with prostate cancer risk in the Japanese population , . Such findings need to be replicated in an independent population sample where the relevant lineages are common. Based on the results of previous population studies, the Japanese appear to have a closer genetic relationship to Koreans than to other Asian populations , ,  so the Korean population is particularly suitable to test for the same correlation.
In the present study, we have therefore investigated the association between Y-chromosomal haplogroups and a predisposition to prostate cancer in the Korean population by examining 106 prostate cancer cases and 110 controls using 14 Y-chromosomal binary markers.
Results and Discussion
We observed eleven different Y-chromosomal lineages defined by the fourteen binary markers in the cancer cases and control samples, most of which are the expected predominant haplogroups in east Asia. Frequency distributions of the fourteen binary markers and corresponding Y-chromosomal haplogroups are listed in Figure 1. The Korean population surveyed here is characterized by a high frequency of haplogroup O-M175 (and its sublineages) in both groups of prostate cancer patients (84.0%) and normal controls (76.3%) (Figure 1 and Table 1). This result is consistent with previous reports, showing that most of the east Asian populations share a common genetic feature of high frequencies of haplogroup O-M175-derived chromosomes , , . The distribution of Y chromosome frequencies studied here was also concordant with previous results from Korean surveys , .
Y-chromosomal haplogroup distribution in prostate cancer cases and controls in the Korean population. The parsimonious tree on the top shows the evolutionary relationship of fifteen haplogroups. Nomenclature is according to the Y Chromosome Consortium . aProstate cancer; bNormal control; Exact P value = 0.44225±0.02442
No statistically significant difference (p<0.05) in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups (Figure 1). We specifically re-investigated the previously-reported associations found in the Japanese population in the Korean samples. Paracchini et al.  reported that haplogroup O-M122-derived lineages (O3 in their paper) were associated with a statistically significant predisposition to prostate cancer in their Japanese sample. We did not find any significant association with prostate cancer risk in our samples of haplogroup O-M122-derived lineages (OR 1.16 (0.68–1.97), p = 0.60; Table 1 ), even though these lineages are more frequent in the Korean population than in the Japanese , , . Neither stratifying by age (<65) nor by disease severity (using the criteria of Paracchini et al. ) led to a significant association (OR 1.50 (0.64–3.50), p = 0.35; OR 1.09 (0.59–2.02), p = 0.77, respectively; Table 2). Ewis et al.  found that haplogroup D/E-YAP was significantly over-represented in their prostate cancer patients and haplogroup O-SRY (including the sublineage O-47z; O2b* and O2b1 respectively in their paper) was significantly under-represented. The absence of the haplogroup D/E-YAP from our Korean sample (0%) made it impossible to assess the correlation between this lineage and the cancer cases (Figure 1). However, we could evaluate the protective effect of the O-SRY lineage. In the Korean sample, no protective effect was seen (OR 1.05 (0.58–1.92), p = 0.87; Table 1). These differences could reflect false positive associations in the previous studies, or a genetic susceptibility expressed by Japanese living in a different environment: the patients examined by Paracchini et al. , for example, were from the US. However, the effects do not seem to be a general feature of east Asian populations since they are not detected in our additional samples from Korea. It is still desirable to study other populations where the lineages are common.
Distribution of the haplogroup O-M122-derived lineages versus all other lineages combined in Korean prostate cancer patients surveyed here
Recent surveys from Asia (e.g., Japan, Singapore and Korea) have shown a general trend of a rising incidence of prostate cancer, although the incidence is still lower in Asia than in Western countries . Seem and Cheng  noted that the increases in age-adjusted mortality rates per 100,000 person-years, adjusted to the world standard, ranged from 50% in Thailand to 260% in Korea. The changing demography of prostate cancer in Asia may be explained by environmental factors. Many Asian countries may be losing their protective dietary habits and acquiring high-risk ones by adopting westernized lifestyles . Thus, further studies with other diverse samples may be required to evaluate joint actions of genetic background and environmental factors for fuller understanding of the oncogenesis of prostate cancer.
Patients and controls
We analyzed a total of 106 Korean prostate cancer patients, who were recruited for the study from the urology department of the Eulji University School of Medicine in Seoul and Daejeon, Korea. Histological classification of prostate cancer was determined according to the World Health Organization (WHO) recommendation and the Gleason pattern. Prostate cancer tissue specimens from all of the patients were collected from frozen samples. In addition, a total of 110 Korean men who had been diagnosed as free of prostate cancer by the Eulji University hospital in Seoul and Daejeon, Korea were recruited as normal controls. These subjects were selected at random (and therefore likely to be unrelated) from the same geographical area as the cases. This study was approved by the Ethics Committee of Eulji Medical Center of the Eulji University School of Medicine in Seoul, and informed consent was obtained from all participants.
DNAs were prepared from the prostate cancer specimens of patients and whole blood samples of controls according to standard methods .
Fourteen Y-chromosomal binary markers were chosen to genotype all individuals sampled: YAP , M7, M9 , RPS4Y711 , SRY+465, DXYS5Y , P31 , M95, M119, M122, M134, M175, M214 , LINE1 . All are known to be polymorphic in east Asia. The Y Alu insertion (YAP), RPS4Y711 (C to T substitution), M9 (C to G substitution), M175 (−5 bp), M95 (C to T substitution), SRY+465 (C to T substitution), DXYS5Y (G to C substitution), and LINE1 insertion were typed using the previously described protocol .
The M7 (C to G substitution), M134 (−1 bp), M214 (T to C substitution), M119 (A to C substitution), P31 (T to C substitution), and M122 (T to C substitution) markers were amplified using the following primer sets and modifications reported by Hammer et al.  and Underhill et al. , : M7, 5′-CTTGACCAATGCCTTGCAAA-3′ and 5′-CAGCCTTGTGATCCAATTA-3′; M134, 5′-AATCATCAAACCCAGAAGGG-3′ and 5′-CCTTGTTAGCTAATTTTGAGC-3′; M214, 5′-TGCTGATACAACACACTGGA-3′ and 5′-AGCCATGGAAATGCCACTTCAC-3′; M119, 5′-GTTATGGGTTATTCCAATTCAGC-3′ and 5′-GAATGCTTATGAATTTCCCAGA-3′; P31, 5′-TAAGGCTGCGTGTTCCCTAT-3′ and 5′-ATATCGTGCCATTGCACACC-3′; M122, 5′-CAGCGAATTAGATTTTCTTGC-3′ and 5′-TGGTAAACTCTACTTAGTTGCCTTT-3′. Each PCR reaction was performed in a total volume of 25 µl containing 25 ng of genomic DNA, 10 pM each primer, 0.2 mM dNTPs, 2.0 mM MgCl2, 50 mM KCl, 10 mM Tris-HCl (pH 8.3), and 1.5 U AmpliTaq DNA polymerase (Perkin-Elmer, Foster, CA, USA). The PCR cycling conditions for the M7 marker used a first denaturation step at 94°C for 5 min, and then 35 cycles at 94°C for 45 sec, 54°C for 45 sec, 72°C for 1 min, and a final extension at 72°C for 3 min. The cycling conditions for the M134 marker used a first denaturation step at 94°C for 5 min, and then 35 cycles at 94°C for 45 sec, 55°C for 45 sec, 72°C for 1 min, and a final extension at 72°C for 3 min. The cycling conditions for the M214 marker used a first denaturation step at 94°C for 5 min, and then 35 cycles at 94°C for 45 sec, 53°C for 45 sec, 72°C for 1 min, and a final extension at 72°C for 3 min. The cycling conditions for M119 were 94°C for 5 min, and then 35 cycles at 94°C for 45 sec, 56°C for 45 sec, 72°C for 45 sec, and a final extension at 72°C for 5 min. P31 was amplified with the PCR conditions of 95°C for 5 min, and then 35 cycles at 94°C for 30 sec, 56°C for 30 sec, 72°C for 45 sec, and a final extension at 72°C for 2 min. The cycling conditions for the M122 marker were 94°C for 5 min, and then 35 cycles at 94°C for 1 min, 54°C for 1 min, 72°C for 1 min, and a final extension at 72°C for 2 min. The PCR products for M122 were digested with Hsp92II enzyme (New England Biolabs, Beverly, MA, USA) and fractionated on 2% agarose gel. Mutations of the M7, M119, M134, M214 and P31 markers were detected by a PCR-SSCP method after PCR amplification described by Kutach et al. . The band patterns of their alleles were evaluated on a 10% native PAGE gel run at 10°C in a cold chamber and visualized by silver staining as described elsewhere .
Y-chromosomal binary haplogroups for all samples of prostate cancer cases and controls were defined by the analysis of all 14 binary polymorphisms. The nomenclature of the haplogroups followed that of the Y chromosome consortium (YCC) .
Y haplogroup frequencies were calculated by counting from the observed phenotypes. To test for significant population differentiation between the prostate cancer cases and the control groups, we used a Chi squared test and Fisher exact test implemented in the Arlequin package version 2.0 . The significance level of the test was applied with a probability of <0.05 as cutoff point. In addition, a test of proportion and odds ratios (OR) with 95% confidence intervals (CI) were also calculated (http://home.clara.net/sisa/).
We would like to thank all volunteers for providing DNA samples for making this study possible. Special thanks go to all the urologists and pathologists in Eulji Medical Center of the Eulji University hospital.
Conceived and designed the experiments: CT WK DS. Performed the experiments: DS HJ KK EK YB. Analyzed the data: CT WK. Contributed reagents/materials/analysis tools: WK TY SK. Wrote the paper: CT WK.
- 1. Brothman AR, Maxwell TM, Cui J, Deubler DA, Zhu XL (1999) Chromosomal clues to the development of prostate tumors. Prostate 38: 303–312.AR BrothmanTM MaxwellJ. CuiDA DeublerXL Zhu1999Chromosomal clues to the development of prostate tumors.Prostate38303312
- 2. Whittemore AS, Lin IG, Oakley-Girvan I, Gallagher RP, Halpern J, et al. (1999) No evidence of linkage for chromosome 1q42.2-43 in prostate cancer. Am J Hum Genet 65: 254–256.AS WhittemoreIG LinI. Oakley-GirvanRP GallagherJ. Halpern1999No evidence of linkage for chromosome 1q42.2-43 in prostate cancer.Am J Hum Genet65254256
- 3. Dagnelie PC, Schuurman AG, Goldbohm RA, Van den Brandt PA (2004) Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies. BJU Int 93: 1139–1150.PC DagnelieAG SchuurmanRA GoldbohmPA Van den Brandt2004Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies.BJU Int9311391150
- 4. Heinlein CA, Chang C (2004) Androgen receptor in prostate cancer. Endocr Rev 25: 276–308.CA HeinleinC. Chang2004Androgen receptor in prostate cancer.Endocr Rev25276308
- 5. Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, et al. (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102: 719–724.JA PetrosAK BaumannE. Ruiz-PesiniMB AminCQ Sun2005mtDNA mutations increase tumorigenicity in prostate cancer.Proc Natl Acad Sci USA102719724
- 6. Jordan JJ, Hanlon AL, Al-Saleem TI, Greenberg RE, Tricoli JV (2001) Loss of the short arm of the Y chromosome in human prostate carcinoma. Cancer Genet Cytogenet 124: 122–126.JJ JordanAL HanlonTI Al-SaleemRE GreenbergJV Tricoli2001Loss of the short arm of the Y chromosome in human prostate carcinoma.Cancer Genet Cytogenet124122126
- 7. Lahn BT, Page DC (1997) Functional coherence of the human Y chromosome. Science 278: 675–680.BT LahnDC Page1997Functional coherence of the human Y chromosome.Science278675680
- 8. McElreavey K, Krausz C, Bishop CE (2000) The human Y chromosome and male infertility. Results Probl Cell Differ 28: 211–232.K. McElreaveyC. KrauszCE Bishop2000The human Y chromosome and male infertility.Results Probl Cell Differ28211232
- 9. Lau YF, Zhang J (2000) Expression analysis of thirty one Y chromosome genes in human prostate cancer. Mol Carcinog 27: 308–321.YF LauJ. Zhang2000Expression analysis of thirty one Y chromosome genes in human prostate cancer.Mol Carcinog27308321
- 10. Dasari VK, Goharderakhshan RZ, Perinchery G, Li LC, Tanaka Y, et al. (2001) Expression analysis of Y chromosome genes in human prostate cancer. J Urol 165: 1335–1341.VK DasariRZ GoharderakhshanG. PerincheryLC LiY. Tanaka2001Expression analysis of Y chromosome genes in human prostate cancer.J Urol16513351341
- 11. Yuan X, Lu ML, Li T, Balk SP (2001) SRY interacts with and negatively regulates androgen receptor transcriptional activity. J Biol Chem 276: 46647–4654.X. YuanML LuT. LiSP Balk2001SRY interacts with and negatively regulates androgen receptor transcriptional activity.J Biol Chem276466474654
- 12. Paracchini S, Pearce CL, Kolonel LN, Altshuler D, Henderson BE, et al. (2003) A Y chromosomal influence on prostate cancer risk: the multi-ethnic cohort study. J Med Genet 40: 815–819.S. ParacchiniCL PearceLN KolonelD. AltshulerBE Henderson2003A Y chromosomal influence on prostate cancer risk: the multi-ethnic cohort study.J Med Genet40815819
- 13. Hammer MF (1995) A recent common ancestry for human Y chromosomes. Nature 378: 376–378.MF Hammer1995A recent common ancestry for human Y chromosomes.Nature378376378
- 14. Jobling MA, Tyler-Smith C (1995) Fathers and sons: the Y chromosome and human evolution. Trends Genet 11: 449–456.MA JoblingC. Tyler-Smith1995Fathers and sons: the Y chromosome and human evolution.Trends Genet11449456
- 15. Jobling MA, Tyler-Smith C (2003) The human Y chromosome: An evolutionary marker comes of age. Nat Rev Genet 4: 598–612.MA JoblingC. Tyler-Smith2003The human Y chromosome: An evolutionary marker comes of age.Nat Rev Genet4598612
- 16. Underhill PA, Passarino G, Lin AA, Shen P, Mirazon Lahr M, et al. (2001) The phylogeography of Y-chromosome binary haplotypes and the origins of modern human populations. Ann Hum Genet 65: 43–62.PA UnderhillG. PassarinoAA LinP. ShenM. Mirazon Lahr2001The phylogeography of Y-chromosome binary haplotypes and the origins of modern human populations.Ann Hum Genet654362
- 17. Hammer MF, Spurdle AB, Karafet T, Bonner MR, Wood ET, et al. (1997) The geographic distribution of human Y chromosome variation. Genetics 145: 787–805.MF HammerAB SpurdleT. KarafetMR BonnerET Wood1997The geographic distribution of human Y chromosome variation.Genetics145787805
- 18. Su B, Xiao J, Underhill P, Deka R, Zhang W, et al. (1999) Y-chromosome evidence for a northward migration of modern humans into eastern Asia during the last Ice Age. Am J Hum Genet 65: 1718–1724.B. SuJ. XiaoP. UnderhillR. DekaW. Zhang1999Y-chromosome evidence for a northward migration of modern humans into eastern Asia during the last Ice Age.Am J Hum Genet6517181724
- 19. Kayser M, Krawczak M, Excoffier L, Dieltjes P, Corach D, et al. (2001) An extensive analysis of Y-chromosomal microsatellite haplotypes in globally dispersed human populations. Am J Hum Genet 68: 990–1018.M. KayserM. KrawczakL. ExcoffierP. DieltjesD. Corach2001An extensive analysis of Y-chromosomal microsatellite haplotypes in globally dispersed human populations.Am J Hum Genet689901018
- 20. Jin HJ, Kwak KD, Hammer MF, Nakahori Y, Shinka T, et al. (2003) Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans. Hum Genet 114: 27–35.HJ JinKD KwakMF HammerY. NakahoriT. Shinka2003Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans.Hum Genet1142735
- 21. Ewis AA, Lee J, Naroda T, Sano T, Kagawa S, et al. (2006) Prostate cancer incidence varies among males from different Y-chromosome lineages. Prostate Cancer Prostatic Dis 9: 303–309.AA EwisJ. LeeT. NarodaT. SanoS. Kagawa2006Prostate cancer incidence varies among males from different Y-chromosome lineages.Prostate Cancer Prostatic Dis9303309
- 22. Hammer MF, Horai S (1995) Y chromosomal DNA variation and the peopling of Japan. Am J Hum Genet 56: 951–962.MF HammerS. Horai1995Y chromosomal DNA variation and the peopling of Japan.Am J Hum Genet56951962
- 23. Horai S, Murayama K, Hayasaka K, Matsubayashi S, Hattori Y, et al. (1996) mtDNA polymorphism in East Asian Populations, with special reference to the peopling of Japan. Am J Hum Genet 59: 579–590.S. HoraiK. MurayamaK. HayasakaS. MatsubayashiY. Hattori1996mtDNA polymorphism in East Asian Populations, with special reference to the peopling of Japan.Am J Hum Genet59579590
- 24. Tajima A, Pan IH, Fucharoen G, Fucharoen S, Matsuo M, et al. (2002) Three major lineages of Asian Y chromosomes: implications for the peopling of east and southeast Asia. Hum Genet 110: 80–88.A. TajimaIH PanG. FucharoenS. FucharoenM. Matsuo2002Three major lineages of Asian Y chromosomes: implications for the peopling of east and southeast Asia.Hum Genet1108088
- 25. Hammer MF, Karafet T, Park H, Omoto K, Harihara S, et al. (2006) Dual origins of the Japanese: common ground for hunter-gatherer and farmer Y chromosomes. J Hum Genet 51: 47–58.MF HammerT. KarafetH. ParkK. OmotoS. Harihara2006Dual origins of the Japanese: common ground for hunter-gatherer and farmer Y chromosomes.J Hum Genet514758
- 26. Hsing AW, Deng J, Sesterhenn IA, Mostofi FK, Stanczyk FZ, et al. (2000) Body size and prostate cancer: a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev 9: 1335–1341.AW HsingJ. DengIA SesterhennFK MostofiFZ Stanczyk2000Body size and prostate cancer: a population-based case-control study in China.Cancer Epidemiol Biomarkers Prev913351341
- 27. Sim HG, Cheng CW (2005) Changing demography of prostate cancer in Asia. Eur J Cancer 41: 834–845.HG SimCW Cheng2005Changing demography of prostate cancer in Asia.Eur J Cancer41834845
- 28. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular Cloning: A laboratory manual, . New York: Cold Spring Harbor Laboratory Press. J. SambrookEF FritschT. Maniatis1989Molecular Cloning: A laboratory manual, 2nd edn.New YorkCold Spring Harbor Laboratory Press 2nd edn.
- 29. Hammer MF (1994) A recent insertion of an Alu element on the Y chromosome is a useful marker for human population studies. Mol Biol Evol 11: 749–761.MF Hammer1994A recent insertion of an Alu element on the Y chromosome is a useful marker for human population studies.Mol Biol Evol11749761
- 30. Underhill PA, Jin L, Lin AA, Mehdi SQ, Jenkins T, et al. (1997) Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography. Genome Res 7: 996–1005.PA UnderhillL. JinAA LinSQ MehdiT. Jenkins1997Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography.Genome Res79961005
- 31. Bergen AW, Wang CY, Tsai J, Jefferson K, Dey C, et al. (1996) An Asian-Native American paternal lineage identified by RPS4Y resequencing and by microsatellite haplotyping. Ann Hum Genet 63: 63–80.AW BergenCY WangJ. TsaiK. JeffersonC. Dey1996An Asian-Native American paternal lineage identified by RPS4Y resequencing and by microsatellite haplotyping.Ann Hum Genet636380
- 32. Shinka T, Tomita K, Toda T, Kotliarova SE, Lee JW, et al. (1999) Genetic variations on the Y chromosome in the Japanese population and implications for modern human Y chromosome lineage. J Hum Genet 44: 240–245.T. ShinkaK. TomitaT. TodaSE KotliarovaJW Lee1999Genetic variations on the Y chromosome in the Japanese population and implications for modern human Y chromosome lineage.J Hum Genet44240245
- 33. Hammer MF, Karafet TM, Redd AJ, Jarjanazi H, Santachiara-Benerecetti S, et al. (2001) Hierarchical patterns of global human Y-chromosome diversity. Mol Biol Evol 18: 1189–1203.MF HammerTM KarafetAJ ReddH. JarjanaziS. Santachiara-Benerecetti2001Hierarchical patterns of global human Y-chromosome diversity.Mol Biol Evol1811891203
- 34. Santos FR, Pandya A, Kayser M, Mitchell RJ, Liu A, et al. (2000) A polymorphic L1 retroposon insertion in the centromere of the human Y chromosome. Hum Mol Genet 9: 421–430.FR SantosA. PandyaM. KayserRJ MitchellA. Liu2000A polymorphic L1 retroposon insertion in the centromere of the human Y chromosome.Hum Mol Genet9421430
- 35. Kutach LS, Bolshakov S, Ananthaswamy HN (1999) Detection of mutations and polymorphisms in the P53 tumor suppressor gene by single-strand conformation polymorphism analysis. Electrophoresis 20: 1204–1210.LS KutachS. BolshakovHN Ananthaswamy1999Detection of mutations and polymorphisms in the P53 tumor suppressor gene by single-strand conformation polymorphism analysis.Electrophoresis2012041210
- 36. Rabilloud T, Carpentier G, Tarroux P (1988) Improvement and simplification of low-background silver staining of protein by using sodium dithionite. Electrophoresis 9: 288–291.T. RabilloudG. CarpentierP. Tarroux1988Improvement and simplification of low-background silver staining of protein by using sodium dithionite.Electrophoresis9288291
- 37. Y Chromosome Consortium (2002) A nomenclature system for the tree of human Y-chromosomal binary haplogroups. Genome Res 12: 339–348.Y Chromosome Consortium2002A nomenclature system for the tree of human Y-chromosomal binary haplogroups.Genome Res12339348
- 38. Schneider S, Roessli D, Excoffier L (2000) Arlequin: A software for population genetics analysis. Version 2.000. Geneva: Genetics and Biometry Lab, Dept of Anthropology, University of Geneva. S. SchneiderD. RoessliL. Excoffier2000Arlequin: A software for population genetics analysis. Version 2.000.GenevaGenetics and Biometry Lab, Dept of Anthropology, University of Geneva