B(A)血型等位基因分型研究

目的了解血清学定型为B(A)血型标本的分子基础。方法采用PCR-SSP方法检测以血清学方法定型为B(A)血型的4名献血者和8例送检患者标本的ABO基因型;对于有O等位基因的杂合子标本,使用特异性引物分别扩增O和B等位基因的7号外显子编码序列,并做测序分析。结果 12例采用血清学方法定为B(A)血型标本的ABO基因型分别为B/B型1例(8.33%),B/O1型4例(33.33%),B/O2型7例(58.33%);序列分析显示:B(A)02等位基因为5例(41.67%),B(A)04等位基因为7例(58.33%)。结论 B(A)04和B(A)02等位基因可能是我国北方汉族人群B(A)血型中主要的遗传类型。     

DNA序列分析法对新的B（A）型等位基因的检测分析

目的：对一ABO血型血清学定型违反一般血型遗传规律的家系进行研究,探讨B（A）血型的鉴定方法和新的B（A）型等位基因检测方法。方法：用血清学血型方法、PCR-SSP法和ABO基因第6及第7外显子直接测序的方法对B（A）血型和B（A）型等位基因进行检测。结果：该家系中血型血清学定型为AB型的成员DNA序列分析测定基因型为B（A）/O型,而PCR-SSP法检测AB型成员的基因型为O/O型。结论：应采用DNA序列分析法才能准确测定汉族人群中B（A）血型,而用PCR-SSP法检测可能引起误诊。     

Mutation of the repeat number of the HPRTB locus and structure of rare intermediate alleles

During routine paternity testing a mutation of a paternal allele at the HPRTB locus was observed. The opportunity was taken to analyse this mutation at a molecular level. The repeat sequence is flanked by an imperfect repeat sequence and this region could be involved in the mutation mechanism. For this reason, we also examined the structure of “intermediate” alleles. Sequencing confirmed the insertion of a perfect repeat motif and revealed a deletion of a dinucleotide some 50 nucleotides downstream from the repeat sequence for the intermediate alleles. It is likely that these intermediate alleles are rare biallelic deletion polymorphisms and are probably not involved in the mutation or variation mechanism of this locus. Received: 22 December 1997 / Received in revised form: 27 April 1998     

110例心肌梗死患者载脂蛋白E基因多态性

为探讨载脂蛋白Ｅ基因型和心肌梗死之间的关系,采用聚合酶链反应－限制性片长多态性分析１１０例心肌梗死患者和１３１例健康对照者的载脂蛋白Ｅ基因型及其在两组人群中的不同分布。结果发现对照组和心肌梗死组Ｅ３／３基因型发生频率最高,占整个样本的７０％,含载脂蛋白Ｅ３的杂合子居中,占整个样本的２５．３％,Ｅ４／４基因型的发生频率最低。     

Detection and analysis of null alleles of amelogenin in gender identification

In this study, we located eight samples with null alleles of amelogenin out of 10,750 cases, and discussed the influence in gender identification and forensic personal identification. Amelogenin was detected and retested by several autosomal STR kits and sex chromosomal STR kits, and the causes were analyzed by chromosome karyotype analysis and Y chromosome microdeletion detection if necessary. Suspected AMEL-X loss was observed in five samples, but no abnormality was detected in the X-STR loci. AMEL-X was recovered when samples were retested by other detection systems designed with different primers. One sample had AMEL-X and X-STR loci loss, and the karyotype was chimeric 45,X0[70]/46,X,+mar[13].Two male samples lost AMEL-Y fragment, and both of them lost DYS522-DYS570-DYS576 loci, but no abnormalities were found in the STS loci of SRY and AZF regions. Therefore, when carrying out gender identification by using amelogenin, it is essential to focus on null alleles of amelogenin. In especially, deal with the samples collected from the individuals who had chromosomal hereditary disorders(e.g. Turner Syndrome and Oligospermia / Azoospermia). In order to achieve this, laboratories should have various techniques to verify the null alleles of amelogenin and ensure accurate genotyping. Accurate genotyping of amelogenin and DNA database establishment are vital for personal identification.     

减低剂量的脐血造血干细胞移植/输注治疗重型再生障碍性贫血21例临床研究

目的观察HLA基因位点不相合的非亲缘脐血造血干细胞移植（简称脐血移植）治疗重型再生障碍性贫血（SAA）的疗效。方法采用3~6个HLA基因位点相合的非亲缘脐血移植/输注治疗重型SAA患者21例。从血缘关系及HLA基因位点、SAA分型、患者体重4个方面进行研究。预处理方案：环磷酰胺50mg·kg^-1·d^-1×2d＋抗人淋巴细胞球蛋白15mg·kg^-1·d^-1/抗胸腺细胞球蛋白3mg·kg^-1·d^-1×5d。应用环孢素A预防移植物抗宿主病（GVHD）。结果5组患者均能达到造血快速重建,总的完全造血重建率达80.98%。根据SAA分型,21例患者中SAA-Ⅰ型16例,15例达到完全造血重建,1例死亡。SAA-Ⅱ型5例,2例完全造血重建,2例部分重建,1例死亡。体重〈60kg的SAA患者13例,11例完全造血重建,2例部分造血重建。体重大于60kg的SAA患者8例,6例完全造血重建,2例死亡。结论脐血移植/输注治疗SAA是一种有效的治疗方法,特别适合于SAA-Ⅰ型的低体重儿童,其配型要求无需十分严格,大体重儿童或成年人应用双份脐血同样可以达到很好的治疗效果。     

抗原处理相关转运体基因与系统性红斑狼疮及自身抗体的相关性

目的 探讨皖籍汉族人群抗原处理相关转运体(transporter associated with antigen processing,TAP)基因与系统性红斑狼疮(systemic lupus erythematosus,SLE)及自身抗体的相关性。方法 应用聚合酶链反应—序列特异性寡核苷酸探针杂交(PCR—SSO))技术对80例SLE患者及96名正常对照人群进行TAP1、TAP2等位基因分型，按实验室常规检测ANA、抗dsDNA、抗RNP、抗Sm、抗SSA、抗SSB抗体。结果 本研究人群的TAP1和TAP2各有4种等位基因型，其频率依次为TAP1*0101＞*020l＞*0301＞*0401，TAP2*0101＞*0201＞*0102＞*0202，有6．8％(12／176)的研究对象用TAPl探针无法定型，10．2％(18／176)TAP2无法定型，呈杂交空白。SLE患者与正常对照人群间TAP等位基因型分布差异无显著性(P＞0．05)。抗RNP抗体与TAP1*0401呈正相关，抗dsDNA及抗SSA抗体与TAP2*0201呈正相关(P＜0．05)。结论 末证明TAP等位基因与SLE的相关性。TAP等位基因与自身抗体的相关性可能和TAP与HLA基因存在连锁不平衡现象有关。     

Estimation of optimal donor number in Bone Marrow Donor Registry: Hong Kong’s experience

Better outcome for hematopoietic stem cell transplantation (HSCT) requires optimal matching between donor and recipient at the HLA-A, -B, -C, and -DRB1 loci. This study estimates the likelihood of identifying HLA matched donors in Hong Kong.7595 volunteer unrelated Chinese donors at the Hong Kong Bone Marrow Donor Registry were typed with HLA-A, -B, -C and -DRB1 genotypes. The matching probabilities for 8/8 and 7/8 HLA match via the matching models were determined.Based on current 100,000 donors in the HKBMDR, the matching probabilities are 45% at 8/8 HLA match and 65% at 7/8 match. By increasing the registry to 200,000, the likelihoods of match become 54% and 73% at 8/8 and 7/8 match stringencies respectively.Our findings may be helpful in planning future donor recruitment and HLA typing. A cost-effective Bone Marrow Donor Registry with a larger pool of donors could increase chance of matching and the success of HSCT.     

Mitochondrial Aldehyde Dehydrogenase Polymorphism in Asian and American Indian Populations: Detection of New ALDH2 Alleles

Genetic deficiency of the mitochondrial aldehyde dehydrogenase (ALDH2) is frequent in Asian peoples where it is an important factor negatively regulating drinking behavior. To obtain additional information on gene geography of known ALDH2 alleles, and look for new variants, ALDH2 genes were evaluated in a Chinese population from Taiwan, a Yakut population of Siberia, and in five North American Indian populations. A novel approach based on a single-strand conformation polymorphism assay, and polymerase chain reaction-directed mutagenesis was developed for genotyping. In the Taiwan Chinese population, the ALDH2² allele frequency was 0.319 ± 0.025, and this allele was not detected in the Yakut population nor in the five North American Indian populations. However, a new allele, ALDH2³ , was detected in Pima Indians at a frequency of 0.044 ±0.022, and this allele was also observed in 1 of 49 Pueblo samples. ALDH2³ is a silent transition 1464 G → A, and it possibly has a wide distribution among North American Indians. A new subtype of the ALDH2² allele, designated as ALDH2^2Taiwan , was found in 1 of 174 Chinese from Taiwan. ALDH2^2Taiwan is characterized by two G → A transitions at bases 1486 and 1510, resulting in Glu → Lys substitutions at both the 479 and 487 positions. Thus, this second nonconservative ALDH2 substitution occurs within the sequence of the already inactive ALDH2² allele.