杨树派间不同种的遗传密码子使用频率分析

遗传密码子的简并性特征造成了不同物种使用的密码子存在偏爱性。了解不同物种的密码子使用特点,可以为外源基因导入过程中的基因改造提供依据,从而实现外源基因的高效表达。杨树是世界上广泛栽培的重要造林树种之一,已经成为林木基因工程研究的模式植物。本研究采用高频密码子分析法,对美洲山杨P.tremuloides,毛白杨P.tomentosa,美洲黑杨P.deltoids和毛果杨P.trichocarpa 4种杨树的蛋白质编码基因序列(CDS)进行了分析,计算出了杨树同义密码子相对使用频率(RFSC),确定了4种杨树的高频率密码子,发现虽然不同种类的杨树密码子使用上有一些差别,但是偏爱密码子的差别却很小,共性的密码子占绝大多数。仅有Pro,Thr和Cys等少数几个氨基酸的偏爱密码子有差别。这种“共性”提示我们,用不同种的杨树中任何一种杨树的偏爱密码子所设计的外源基因在其他杨树中也可以使用。     

应用mAPLP方法分析湖南汉族、苗族和土家族mtDNA编码区多态性

为建立线粒体DNA编码区SNP快速分型方法, 在线粒体DNA编码区选取16个SNP位点(5178A、10398A、14979C、 8020A、 13104G、11959G、10400T、14178C、3970T、5417A、11969A、12811C、10873T、4580A、7028C、12612G), 采用多重扩增产物片段长度多态性分析方法, 对湖南地区汉族、苗族和土家族各100人进行了mtDNA编码区多态性分析。结果显示SNP 3970T在汉族和土家族人群中的分布频率(均为17%)与苗族相比(8%)存在明显差异(P＜0.01), SNP 8020A在汉族人群中的分布频率(6%)与苗族和土家族人群( 分别为2%和0%)相比存在差异( P＜0.05)。在所分析的300名个体中, 共检测到45种单倍型, 3个民族共有的单倍型12种, 两个民族共有的有10种, 有23种单倍型仅在1个民族中出现, 其中汉族特异性的单倍型有8种, 苗族特异性的有6种, 土家族特异性的单倍型有9种。mAPLP是通过设计两条不同的正向或反向引物(使PCR扩增片段长度不同)和1条共用的反向或正向引物, 使两个等位特异扩增片段大小不同, 从而达到SNP分型。     

贵州四个民族人群线粒体DNA编码区的多态性

目的研究贵州土家族、侗族、仡佬族和彝族人群线粒体DNA（mtDNA）编码区的核苷酸多态性。方法采用PCR-RFLP技术和DNA测序法对贵州4个群体145例样本mtDNA编码区的8个SNP基因座及COⅡ/tRNAlys基因间9 bp缺失进行多态性分析。结果贵州4个民族群体的9 bp缺失频率依次为土家族18.4%,侗族29.7%,仡佬族25%,彝族16.7%,平均缺失频率为22.8%;在8个SNP基因座中,A10398G、C10400T突变在4个群体中较普遍;A663G、C5178A和G12406A突变在部分民族群体中也有较高的频率;共检测出14种单倍型,其中仡佬族11种,土家族10种,侗族8种,彝族6种。结论贵州4个民族群体mtDNA编码区可能存在不同的突变热点,在等位基因和单倍型分布频率上存在一定差异。     

三角帆蚌GPX基因结构特征及抗性相关SNP的筛选

根据三角帆蚌(Hyriopsis cumingii)谷胱甘肽过氧化物酶(Glutathione peroxidase,GPX)基因cDNA序列,通过PCR和基因组步移法,从三角帆蚌基因组DNA中扩增出GPX基因全长及其5′调控区。序列分析表明,该基因序列全长6 708 bp,含有2个外显子,1个内含子。5′调控区为992 bp,含有启动子的核心序列TATA盒以及其他一些转录调控元件,如AP1、C/EBP、CdxA。2个外显子长度分别为273 bp和991 bp,内含子长度为4 491 bp。通过直接测序法在三角帆蚌抗性群体和易感群体中筛选GPX基因的SNPs,并研究这些多态性位点与抗逆性状的相关性。共获得了16个SNP位点,其中启动子区的A-99G位点、A-86C位点、A-49C位点,内含子区的A2841T位点、C2847T位点、G3146C位点、A3150G位点以及G4645T位点共8个SNP位点的基因型频率和等位基因频率在抗性和易感群体中均存在显著性差异(P<0.05)。连锁不平衡分析结果显示GPX基因A-86C位点、A-49C位点、C2847T位点、A3150G位点与G4645T位点之间,以及A2841T位点与G3146C位点之间均存在强连锁不平衡。同时单倍型分析发现,在抗性群体中单倍型分别为ACTGT和TG的个体出现的频率显著高于易感群体中出现的频率。这些结果表明,GPX基因的部分SNPs可作为三角帆蚌抗病辅助育种的候选分子标记。     

INCENP基因功能性单倍型可调控启动子活性并影响公牛精液品质

为研究内着丝粒蛋白(Inner centromere protein, INCENP)基因启动子区单核苷酸多态性(SNPs)与精液品质的相关性,本文利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测了250头中国荷斯坦公牛INCENP基因的基因型。在INCENP基因启动子区鉴定出两个SNPs (g.-556 G>T,rs 136823901和g.-692 C>T,rs 211010999),发现了3种单倍型(CG、TT、TG)。分析两个SNP位点的基因型频率和等位基因频率,各SNP及单倍型组合与中国荷斯坦公牛精液品质的相关性,结果表明SNP位点g.-556 G>T GT基因型个体的鲜精活力显著高于GG基因型个体(P<0.05),单倍型组合H1H1(CCGG)、H1H3(CTGT)、H2H3(TTGT)和H3H3(TTTT)个体的鲜精活力和冻精解冻后活力均显著高于H1H2个体(P<0.05)。为进一步研究g.-556 G>T和g.-692 C>T影响精液品质的可能机理,本文将3种单倍型质粒分别转染小鼠睾丸间质细胞(MLTC-1),结果显示含TG单倍型的载体荧光素酶活性最高。由此推测,g.-556 G>T和g.-692 C>T为启动子区功能性突变位点,可通过调节启动子活性来调控INCENP基因表达,进而影响精液品质。     

牦牛TMEM-18基因多态性及其与生产性能关联分析

跨膜蛋白18基因(TMEM-18)是一个末端为低聚嘧啶的基因,与动物生长发育密切相关。为了研究牦牛TMEM-18基因多态性与生产性能的关系。以192头天祝雌性牦牛血样NDA构建混合池,扩增TMEM-18基因内含子1和外显子5的序列。运用BLAST和Chromas软件分析突变位点,运用高分辨率熔解曲线分析技术(HRM)统计基因型分型,采用SHEsis软件进行基因型频率和等位基因频率计算,同时对多态位点进行配对连锁不平衡和单倍型分析,运用SPSS21.0分析基因多态位点与生产性能关联。结果表明,牦牛TMEM-18基因内含子1处存在2个多态位点,分别是861(A/G)和1267(C/T),外显子5处存在1个多态位点为4 447(C/T)。关联分析表明,牦牛TMEM-18基因861(A/G)位点的不同基因型与牦牛的体高、体重、胴体重和屠宰率差异性显著(P0.05);1267(C/T)位点的不同基因型与牦牛的体高、体重和屠宰率差异性显著(P0.05),而牦牛TMEM-18基因4447(C/T)位点的不同基因型与牦牛的体斜长、管围、胸围、体重、胴体重、净肉重、净肉率和屠宰率均存在显著性差异(P0.05)。通过单倍型分析发现群体中存在3种单倍型组合,即ACC单倍型、GTC单倍型和GTT单倍型,其中ACC单倍型组合个体数目明显多于其他单倍型组合,为优势单倍型。本实验揭示TMEM-18基因可作为牦牛生产性能开发的候选分子标记,为牦牛遗传资源的利用、开发与新品种的选育提供依据。     

3个鸡种GARS-AIRS-GART基因第21号外显子的SNPs检测

采用PCR-SSCP和DNA测序法对安卡鸡、文昌鸡和如皋鸡中GARS-AIRS-GART基因的第21号外显子进行SNPs检测.结果发现该外显子含4个核苷酸多态位点:G29943A、C29968T、T30011C和C30017T,其中3处为非同义突变,分别为:29 943处天冬氨酸(Asp)→天冬酰胺(Asn)、30 011处色氨酸(Trp)→精氨酸(Arg)、30 017处精氨酸(Arg)→半胱氨酸(Cys);另一处为同义突变.对多态位点进行单倍型分析,发现12种单倍型,其中两种单倍型(5号和6号)的频率超过10%,分别为0.330 0和0.162 8,1号、3号、9号和10号单倍型频率介于1%～10%之间,其余都小于1%.另外共检测到11种基因型,存在5种等位基因,安卡鸡的D和E等位基因的基因频率较高,基因型与其它两个鸡品种之间都存在着极显著的差异(P<0.01),表明我国地方鸡种和外来鸡种在遗传组成上存在着差异.本研究将为鸡肉品质相关研究积累基础数据,为今后深入开展肉品质的开发利用奠定理论基础.     

意大利蜜蜂染色体DNA非编码区抗白垩病相关的SNP的筛选与验证

【目的】筛选验证意大利蜜蜂Apis mellifera ligustica染色体DNA非编码区与抗白垩病相关的SNP。【方法】本研究将蜜蜂球囊菌Ascosphaera apis孢子接种于人工饲养的意大利蜜蜂3日龄幼虫,根据是否存在白垩病症状进而筛选出抗病个体和易感个体。基于前期重测序结果中意大利蜜蜂第2和11号染色体DNA非编区与抗白垩病相关的SNP信息,利用PCR测序的方法筛选并验证意大利蜜蜂幼虫第2和11号染色体DNA非编码区与幼虫抗白垩病相关的55个SNP。【结果】发现位于意大利蜜蜂第11号染色体LOC100578413基因5′端的非编码区的SNP(T14570310C)在抗病个体中T等位基因频率高于C等位基因频率,且抗病个体中的T等位基因频率显著高于易感幼虫中的T等位基因频率,表明该SNP位点与抗白垩病相关。该分子标记对抗性个体和易感个体的判断结果与前期筛选的编码区SNP(C2587245T)分子标记的结果一致。【结论】筛选并验证意大利蜜蜂第11号染色体DNA非编码区的SNP(T14570310C)与抗白垩病相关。该位点为抗白垩病分子辅助选育提供新的分子标记,在意大利蜜蜂白垩病早期检测和培育白垩病抗性的蜂种方面具有重要意义。     

基于线粒体细胞色素b基因全序列的海南长臀鮠南渡江种群遗传变异分析

测定了海南南渡江15尾海南长臀鮠(Cranoglanis bouderius multiradiatus)的cytb基因全序列1138bp,发现3个可变位点和1个简约信息位点,共检测到4种单倍型。海南长臀鮠Cytb基因具有典型的起始密码子(ATG)和不完全终止密码子(T^**),共编码379个氨基酸,密码子第三位点G的含量仅2.9%,而C和A的含量分别为39.1%和38.5%,在第二位点上T的使用频繁高达41.3%,表明cytb基因在密码子碱基的使用具有偏倚性。海南长臀鮠基于Kimura-2-parameter模型的单倍型间遗传距离为0.0009～0.0017,在NJ系统树中没有明显的谱系结构,单倍型多样性(0.600)和核苷酸多样性(0.0006)都较低,表明海南长臀鮠遗传多样性非常贫乏,应及时采取有效措施保护海南南渡江种群。     

青海高原牦牛mtDNA Cytb基因和D-loop区遗传多样性及系统进化分析

为探究青海高原牦牛的遗传多样性和起源进化关系,本研究通过测定和分析青海高原牦牛155个个体细胞色素b基因(Cytb)和D-loop区全序列,分析多态性及构建系统进化树.结果表明:青海高原牦牛Cytb基因全序列长度为1 140 bp,个体间序列长度无差异,4种核苷酸T、A、G、C的含量分别为26.26％、31.73％、13.09％、28.920％;发现13个SNP位点,全部为转换,符合Cytb基因保守的特征;核苷酸多样性(Pi)为0.002 88,单倍型数(H)为9,单倍型多样性(Hd)为0.645;D-loop区序列长度在892～895 bp之间,不同个体间存在序列长度差异;4种核苷酸T、A、G、C的平均比例分别为28.69％、32.22％、13.75％、25.34％,A+T含量为60.91％,G+C含量为39.09％.在155个个体中共统计出41个SNP位点,其中转换38个,颠换3个,缺失5个,插入3个.其核苷酸多样性(Pi)为0.012 44,分析得到的单倍型数(H)为38,单倍型多样性(Hd)为0.881.在基于Cytb基因的系统进化树中,青海高原牦牛首先与野牦牛和巴州牦牛聚在一起,紧接着与美洲野牛聚在一起;在D-loop区的系统进化分析中,青海高原牦牛首先与西藏牦牛和野牦牛聚在一起,展示出丰富的遗传多样性,同时进一步支持了牦牛和野牦牛划为牛亚科牦牛属(Bovidae)的观点.本研究结果为牦牛改良及育种工作提供了科学依据.     

Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls

Brunner et al. (1993, Science 262, 578-580) reported a family in which several males were affected by a syndrome of borderline mental retardation and abnormal behavior. Sequencing of exon 8 of the MAO-A gene revealed a mutation that results in a termination codon and was associated with the syndrome in the family. To determine the possible role of any mutation in exon 8 of the MAO-A gene in susceptibility to alcoholism associated with antisocial personality (ASP), we sequenced genomic DNA from 50 alcoholics and 50 normal controls. We detected only the point mutation at the position 941 (T --> G). Additional samples of alcoholics and normal controls were also screened for this mutation and the mutation in exon 14 by PCR assays. Comparison of alcoholics with ASP to normal controls for both mutation frequencies in exons 8 and 14 was positive. However, the haplotype frequency differences in the above groups were borderline significant. The most common haplotype between these mutations and a (CA)n repeat marker in the gene was F1E,C6. The frequency differences between alcoholics with ASP and normal controls for this haplotype were significant (P = 0.033). In TDT analysis, comparison of the overall haplotypes, transmitted to nontransmitted, was borderline significant. These data indicate that mutations in the MAO-A gene may play a role in the development of alcoholism associated with ASP.     

Novel PKU mutation on haplotype 2 in French-Canadians.

We analyzed DNA from nine French-Canadian probands from eastern Quebec province; all had hyperphenylalaninemia (phenylketonuria [PKU] or non-PKU forms) caused by mutations at the phenylalanine hydroxylase locus. Analysis of RFLP haplotypes and mutations revealed a novel mutation, an A-to-G transition (met----val) in codon 1 (the translation-initiation codon). It occurred on 5 of the 18 mutant chromosomes and was associated each time with haplotype 2. A proband homozygous for this mutation had the PKU phenotype. In other probands, the codon 1 mutation was inherited once with the splice junction mutation in exon 12 (on haplotype 3), conferring PKU, and was inherited twice with a mutation on haplotype 1, conferring PKU in one proband and non-PKU hyperphenylalaninemia in the other. The other five probands carried mutations, conferring PKU, on the following haplotype combinations: 1/3 (twice), 1/9, 3/4, and 1/1. The mutations on haplotypes 1, 4, and 9 are not yet characterized. This preliminary study reveals a novel PKU mutation and considerable genetic heterogeneity at the phenylalanine hydroxylase locus in French-Canadians.     

Polymorphism of the HFE gene associated with hereditary hemochromatosis in populations of Russia

Expression of hereditary hemochromatosis as well as predisposition to iron overload syndrome and sporadic porphyria cutanea tarda are currently believed to be associated with the inheritance of certain allelic variants of the HFE gene. Allele frequencies of the C282Y (845A) and H63D (187G) mutations in the HFE gene in human populations of different races are remarkably different, and the prevalence of the S65C (193T) mutation is still poorly studied. In the present study we estimated allele frequencies of HFE mutations in Russians and in a number of Siberian ethnic indigenous populations. In Russians, allele frequencies of the C282Y, H63D and S65C mutations were 3.7, 13.3 and 1.7%, respectively. These values were similar to those observed in populations of Europe. The C282Y mutation was not detected in the population samples of Siberian ethnic groups, including Mansis, Khantys (Finno-Ugric group), Altaians, and Nivkhs (Mongoloids), suggesting that the frequency of this allele in the populations examined was lower than 1%. The frequency of the C282Y allele in the Tuvinian and Chukchi samples (Mongoloids) constituted 0.45 and 0.8%, respectively. Furthermore, pedigree analysis of both Chukchi carriers discovered showed that some of their ancestors were from other ethnic groups. Low frequencies of this allelic variant is typical of many Eastern Asian populations, which are also characterized by rather low frequencies of the H63D variant. In contrast, in some ethnic groups of Western Siberia allelic frequency of the H63D mutation is rather high, constituting 8.7% in Altaians, 15.5% in Mansis, and 11.3% in Khantys. The frequency of this allele in Tuvinians, Nivkhs, and Chukchis constituted 5, 4.7, and 0.8%, respectively. These findings make it possible to estimate the proportion of individuals predisposed to iron overload syndrome in different Russian ethnic groups. The HFE allele frequency distribution patterns observed in the populations examined pointed to pre-Celtic appearance of the CY82 allele. It also provides elucidation of the evolutionary genetic relationships between Siberian ethnic groups and the contemporary populations of Eastern and Western Europe.     

Novel mutations of endothelin-B receptor gene in Pakistani patients with Waardenburg syndrome

Mutations in EDNRB gene have been reported to cause Waardenburg-Shah syndrome (WS4) in humans. We investigated 17 patients with WS4 for identification of mutations in EDNRB gene using PCR and direct sequencing technique. Four genomic mutations were detected in four patients; a G to C transversion in codon 335 (S335C) in exon 5 and a transition of T to C in codon (S361L) in exon 5, a transition of A to G in codon 277 (L277L) in exon 4, a non coding transversion of T to A at −30 nucleotide position of exon 5. None of these mutations were found in controls. One of the patients harbored two novel mutations (S335C, S361L) in exon 5 and one in Intronic region (−30exon5 A>G). All of the mutations were homozygous and novel except the mutation observed in exon 4. In this study, we have identified 3 novel mutations in EDNRB gene associated with WS4 in Pakistani patients.     

Screening for mutations of the apolipoprotein B gene causing hypocholesterolemia

In this study we have performed analyses of apolipoprotein (apo) B at both the protein and gene level to search for mutations of the apoB gene causing hypocholesterolemia among 71 Norwegian subjects. None of the subjects possessed apoB of abnormal molecular weight as determined by SDS-polyacrylamide gel electrophoresis of lipoproteins in the 1.025 g/ml–1.063 g/ml density range. Screening for mutations in exon 26 of the apoB gene by analysis of single-strand conformation polymorphisms followed by DNA sequencing, revealed seven point mutations of which one is a novel mutation. Five of the mutations were missense mutations and two were sense mutations. A group of 143 hypercholesterolemic, nonfamilial hypercholesterolemia subjects served as a control group for comparisons of gene frequencies. The only statistically significant finding was that mutation 8344T at codon 2712 was more common among those with hypocholesterolemia. This finding is in accord with previous reports. Received: 20 January 1997 / Accepted: 25 September 1997     

中国广东汉族人群核苷酸修复基因hMTH1 遗传多态性研究

为研究中国南方汉族人群核苷酸修复基因hMTH1遗传多态性,应用聚合酶链反应-单链构象多态性技术检测172名健康人外周血白细胞hMTH1基因启动子及全部5个外显子多态性,并进行DNA测序。结果发现hMTH1基因启动子及外显子1序列保守,未见突变;外显子2第73位碱基存在T→C杂合型突变,基因型TT和TC频率分别为93.02%、6.98%,等位基因T和C频率分别为96.51%、3.49％;外显子3第45位遗传密码存在T→C杂合型突变,基因型TT和TC频率分别为95.35%、4.65%,等位基因T和C频率分别为97.67%、2.33%,该多态性为首次发现;外显子4第83位遗传密码存在G→A杂合型突变,基因型GG和GA频率分别为89.53%、10.47%,等位基因G和A频率分别为94.77%、5.23％;外显子5第119位氨基酸遗传密码存在C→T杂合型突变,基因型CC和CT频率分别为95.93%、4.07%,等位基因C和T频率分别为97.97%、2.03％。Abstract: In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene’s promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49％, respectively. A T to C polymorphism was detected at codon 45 in exon3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23％, respectively. A C to T polymorphism was detected at codon 119 in exon5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03％, respectively.     

Two mutations within the coding sequence of the phenylalanine hydroxylase gene

Summary Two previously unidentified mutations at the phenylalanine hydroxylase locus were found during a study of the relationship between genotype and phenotype in phenylketonuria and hyperphenylalaninemia. One mutation eliminates the BamHI site in exon 7 and the other eliminates the HindIII site in exon 11 of the phenylalanine hydroxylase gene. They were suspected because of deviating restriction fragment patterns and confirmed by amplification, via the polymerase chain reaction, of exon 7 and exon 11, respectively, followed by digestion with the appropriate restriction enzyme. Direct sequencing of amplified mutant exon 7 revealed a G/C to T/A transversion at the first base of codon 272, substituting a GGA glycine codon for a UGA stop codon. Direct sequencing of amplified mutant exon 11 revealed a deletion of codon 364, a CTT leucine codon. The exon 7 mutation can be expected to result in a truncated protein and the exon 11 mutation in the elimination of an amino acid in the catalytic region of the enzyme. A patient who is a compound heterozygote for these two mutations has classical phenylketonuria. It is concluded that each of the two mutations leads to a profound loss of enzymatic activity. The segregation of these mutations with disease alleles in 4 and 2 families, respectively, supports the hypothesis that multiple mutations at the phenylalanine hydroxylase locus explain the variable phenylalanine tolerance in patients with phenylalanine hydroxylase deficiency.     

Analysis of the hemochromatosis gene (HFE) mutations, C282Y and H63D, in the populations of Central Asia

Analysis of the C282Y and H63D mutations in the HFE gene was carried out in 594 individuals representing seven indigenous populations of Central Asia. Among the populations examined, mutation C282Y was found in Uighurs with the frequency of 0.009, and in Kazakhs and Tajiks with the frequency of 0.012. The mutation was absent in Uzbeks, Kyrgyzes, Kurds, and Turkmens. Mutation H63D was detected in all populations studied with the frequencies ranging from 0.024 (Tajiks) to 0.139 (Turkmens). Judging by the frequencies of the mutations of interest, the populations examined occupied the intermediate position between the European and Eastern Asian populations, which corresponded to their geographical position.     

PKU in Slovakia: mutation screening and haplotype analysis

The restriction fragment length polymorphism haplotypes and seven common mutations in the phenylalanine hydroxylase gene were analysed in 49 unrelated Slovak phenylketonuria (PKU) families of Caucasian origin. The predominant mutation in this population sample is R408W, with a frequency of 45.9%. In addition, four other mutations have been identified at relatively high frequencies: IVS12nt1, 10.2%; R158Q, 7.1%; R261Q, 7.1%; R252W, 2.0%. The mutation-haplotype associations correspond to those described in other European populations. The high proportion of mutations (72.4%) amenable to simple rapid detection based on the polymerase chain reaction provides a good basis for direct DNA-diagnosis of PKU in the Slovak population.     

Incidence of fibroblast growth factor receptor 3 gene (FGFR3) A248C, S249C, G372C, and T375C mutations in bladder cancer

Bladder cancer is the most frequent cancer of the urinary system. Fibroblast growth factor receptors (FGFR) belong to the tyrosine kinase family and have important roles in cell differentiation and proliferation and embryogenesis. FGFR3 is located on chromosome 4p16.3, and missense mutations of FGFR3 are associated with autosomal dominant human skeletal disorders and have some oncogenic effects. We examined the incidence of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, and their correlation with clinical-pathological parameters in bladder carcinoma patients. Fifty-six paraffin-embedded specimens of transitional cell carcinoma of the urinary bladder were included in this study. Analysis of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, was performed by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, were detected in 33 of the 56 patients (heterozygous mutant). Among the 56 transitional cell carcinomas, missense point mutations were detected in seven of them at codon A248C, 28 of them at codon S249C, and three of them at codon T375C, similar to data from previous reports. When the results of the FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C and in exon 10, G372C and T375C, were analyzed one by one or as a group, despite the findings of previous research reports, our data suggest that these mutations are detected homogenously regardless of the tumor classification and tumor grade.