Genetic affinities of north and northeastern populations of India: inference from HLA-based study

India is like a microcosm of the world in terms of its diversity; religion, climate and ethnicity which leads to genetic variations in the populations. As a highly polymorphic marker, the human leukocyte antigen (HLA) system plays an important role in the genetic differentiation studies. To assess the genetic diversity of HLA class II loci, we studied a total of 1336 individuals from north India using DNA-based techniques. The study included four endogamous castes (Kayastha, Mathurs, Rastogies and Vaishyas), two inbreeding Muslim populations (Shias and Sunnis) from north India and three northeast Indian populations (Lachung, Mech and Rajbanshi). A total of 36 alleles were observed at DRB1 locus in both Hindu castes and Muslims from north, while 21 alleles were seen in northeast Indians. At the DQA1 locus, the number of alleles ranged from 11 to 17 in the studied populations. The total number of alleles at DQB1 was 19, 12 and 20 in the studied castes, Muslims and northeastern populations, respectively. The most frequent haplotypes observed in all the studied populations were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1501-DQA1*0103-DQB1*0601. Upon comparing our results with other world populations, we observed the presence of Caucasoid element in north Indian population. However, differential admixturing among Sunnis and Shias with the other north Indians was evident. Northeastern populations showed genetic affinity with Mongoloids from southeast Asia. When genetic distances were calculated, we found the north Indians and northeastern populations to be markedly unrelated.     

Characterization and sequence analysis of the novel HLA-Cw*040105 allele in a Chinese Uygur individual

A novel human leukocyte antigen (HLA) allele, HLA-Cw*040105, was identified in a Chinese Uygur individual. It differs from the closest allele Cw*04010101 by four nucleotides at position nt 60 (C>T) in exon 1, genomic nt 477 (A>T) in intron 2, nt 835(T>C), and nt 850 (C>T) in exon 3.     

A novel HLA-B*57 (B*5714) allele in a healthy male Caucasian individual

A novel human leucocyte antigen (HLA)-B57 (HLA-B*5714) allele has been identified in a male Caucasian individual from Middle Europe using single allele-specific sequencing strategy. This allele is identical to the HLA-B*570101 allele except for two point mutations in exon 3 at codon 138 (ACG→ACC) with no amino acid change [persisting threonine (T)] and at codon 171 (TAC→CAC), resulting in an amino acid change from tyrosine (Y) to histidine (H).     

Twenty-three novel alleles increase diversity at the HLA-C locus

Twenty-three novel HLA-C alleles are described. Nine of the new alleles are single-nucleotide substitutions from their most homologous allele of which seven result in amino acid changes (Cw*0327, *0508, *0514, *0613, *0735, *0739 and *1517) and two are silent substitutions (Cw*030305 and *070107). The remaining 14 alleles (Cw*0113, *0207, *0212, *0216, *0318, *0411, *0417, *0512, *0722, *0733N, *1216, *1218, *1515 and *1607) differ from their most similar alleles by 2-4 nucleotide substitutions that result in 1-3 amino acid differences.     

Two novel alleles HLA-B*9536 and B*4612 were identified in a healthy Chinese individual

The novel HLA-B*9536 and B*4612 alleles were identified by sequence-based typing in China.     

DRB1*1613N: a novel DRB1 allele with a premature termination codon

DRB1 null alleles are extremely rare and always sporadic, suggesting their biological selective disadvantage.     

Genetic background of IL-10(-/-) mice alters host-pathogen interactions with Campylobacter jejuni and influences disease phenotype

We hypothesized that particular genetic backgrounds enhance rates of colonization, increase severity of enteritis, and allow for extraintestinal spread when inbred IL-10(-/-) mice are infected with pathogenic C. jejuni. Campylobacter jejuni stably colonized C57BL/6 and NOD mice, while congenic strains lacking IL-10 developed typhlocolitis following colonization that mimicked human campylobacteriosis. However, IL-10 deficiency alone was not necessary for the presence of C. jejuni in extraintestinal sites. C3H/HeJ tlr4(-/-) mice that specifically express the Cdcs1 allele showed colonization and limited extraintestinal spread without enteritis implicating this interval in the clinical presentation of C. jejuni infection. Furthermore, when the IL-10 gene is inactivated as in C3Bir tlr4(-/-) IL-10(-/-) mice, enteritis and intensive extraintestinal spread were observed, suggesting that clinical presentations of C. jejuni infection are controlled by a complex interplay of factors. These data demonstrate that lack of IL-10 had a greater effect on C. jejuni induced colitis than other immune elements such as TLR4 (C3H/HeJ, C3Bir IL-10(-/-)), MHC H-2g7, diabetogenic genes, and CTLA-4 (NOD) and that host genetic background is in part responsible for disease phenotype. C3Bir IL-10(-/-) mice where Cdcs1 impairs gut barrier function provide a new murine model of C. jejuni and can serve as surrogates for immunocompromised patients with extraintestinal spread.     

Transseptal Left Ventricular Lead Placement Using Snare Technique

Background: Coronary sinus (CS) lead placement for cardiac resynchronization therapy has a failure rate of ～5–10%. Here we describe a way of implanting an endocardial left ventricular (LV) lead via a transseptal puncture (TSP), using a GooseNeck snare and active fixation lead. Methods: Three male patients (67–83 years) with failed or extracted epicardial LV leads implanted via the CS had an endocardial LV lead implanted. TSP was performed via a femoral vein. The active fixation pacing lead was advanced to the right atrium from a subclavian vein. A GooseNeck snare was passed via the TSP sheath and used to grasp the tip of the pacing lead. The sheath, GooseNeck snare, and pacing lead tip were then passed to the left atrium by sliding the system up the TSP guidewire and across the interatrial septum before deflecting the lead to permit implantation in the left ventricle. Results: Successful implantation was performed in all patients with an LV implant time of 25–55 minutes. Conclusion: The use of a GooseNeck snare via a deflectable transseptal sheath represents a reliable alternative method for endocardial LV lead placement in patients with failed CS LV lead implantation. (PACE 2012; 35:1248–1252)     

人类白细胞抗原新等位基因HLA-A*31∶22的序列分析及确认

目的 序列分析及确认一例中国人群中的人类白细胞抗原(human leukocyte antigen,HLA)新等位基因.方法 应用基于Luminex平台的聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)基因分型法、PCR产物测序法和组特异性引物测序法,通过软件分析该样本DNA基因序列及与最相近HLA等位基因序列的差异.结果 PCR-SSOP结果显示该样本HLA-A基因座的反应格局与已知HLA-A等位基因均不一致;DNA序列分析显示,在所检测的第2～4外显子中,该样本HLA-A基因座序列与所有已知HLA-A等位基因序列均不一致,与同源性最高的等位基因A*31∶01∶02的差异只在外显子2区域中产生了nt 245 A—C一个碱基取代,并导致相应的82位密码子由GAG→GCG,编码的氨基酸由谷氨酸(Glu)变为丙氨酸(Ala).结论 该基因为HLA新等位基因,被世界卫生组织HLA因子命名委员会正式命名为HLA-A*31∶22.     

HLA-DRB1和HLA-DQB1基因多态性与天疱疮的相关性

目的探讨人白细胞抗原(HLA)-DRB1和HLA-DQB1等位基因多态性与天疱疮的遗传相关性。方法以上海地区的58例天疱疮患者(病例组)和89名正常对照者(对照组)作为研究对象。采用聚合酶链反应-序列特异性引物分型技术(PCR-SSP)对两组HLA-DRB1和HLA-DQB1等位基因进行分型,直接计数法计算等位基因频率并进行组间比较,以等位基因频率的比值比(OR)评价基因与疾病的关联性。结果病例组和对照组共检测到13种HLA-DRB1等位基因和5种HLA-DQB1等位基因。统计学分析结果表明:病例组HLA-DRB1*14和HLA-DQB1*05等位基因频率分别为17.24%和18.97%,显著高于对照组的1.69%(P=0.000,P值的校正值Pc<0.05,OR=12.150)和6.74%(P=0.001,Pc<0.05,OR=3.238);病例组HLA-DQB1*06等位基因频率为15.52%,显著低于对照组的30.90%(P=0.003,Pc<0.05,OR=0.411)。结论 HLA-DRB1*14和HLA-DQB1*05可能是上海地区天疱疮患者的易感基因,而HLA-DQB1*06则可能是保护基因。