Commentary: meta-analysis of individual participants' data in genetic epidemiology

The authors summarize their experience in the conduct of meta-analysis of individual participants' data (MIPD) with time-to-event analyses in the field of genetic epidemiology. The MIPD offers many advantages compared with a meta-analysis of the published literature. These include standardization of case definitions, outcomes, and covariates; inclusion of updated information; the ability to fully test the assumptions of time-to-event models; better control of confounding; standardization of analyses of genetic loci that are in linkage disequilibrium; evaluation of alternative genetic models and multiple genes; consistent treatment of subpopulations; assessment of sampling bias; and the establishment of an international collaboration with the capability to prospectively update the meta-analyses and synthesize new information on multiple genetic loci and outcomes. The disadvantages of a MIPD compared with a meta-analysis of the published literature are that a much greater commitment of time and resources is required to collect primary data and to coordinate a large collaborative project. An MIPD may collect additional, unpublished data, but it is possible that not all published data may be contributed at the individual level. For questions that justify the required intensive effort, the MIPD method is a useful tool to help clarify the role of candidate genes in complex human diseases.     

Identification of single nucleotide variations in the coding and regulatory regions of the myelin-associated glycoprotein gene and study of their association with multiple sclerosis

The myelin-associated glycoprotein (MAG) gene is an appealing candidate in the 19q13 Multiple Sclerosis (MS) candidate region. Using denaturing high performance liquid chromatography (DHPLC), we identified 14 single nucleotide polymorphisms (SNPs) in MAG coding and regulatory regions, and we tested their possible association with MS in Italian patient and control DNA pools. Eight variations had a frequency <0.05, i.e. below the detection limit in the pools. Of these, Arg537Cys was further studied with individually genotyped individuals and was detected in 1/189 patients and 0/85 controls. The frequency of the six remaining SNPs were not significantly different in pools including a total of 1266 patient and 1612 control chromosomes. Considering the statistical power of the experimental design, these results exclude the MAG gene as an MS susceptibility factor with an odds ratio (OR) equal or higher than 1.3.     

RPE细胞光损伤相关新基因s-lap编码区克隆及s-lap/GFP融合蛋白在B16黑色素瘤细胞中的表达与定位

目的 克隆新基因s-lap编码区序列，研究其编码的蛋白质在B16黑色素瘤细胞内的表达与定位。方法 分析s-lap cDNA序列，建立视网膜色素上皮(retinal pigment epithelium，RPE)细胞光损伤模型，RT-PCR克隆其编码区序列，构建了带有绿色荧光蛋白的目的基因真核表达重组质粒pcDNA3.1-GFP/s-lap，转染B16黑色素瘤细胞，观察s-lap／GFP融合蛋白在B16黑色素瘤细胞内的表达与定位。结果 s-lap cDNA序列含有编码101个氨基酸的开放读码框架，有2个可能的N-糖基化位点，1个可能的casein kinase Ⅱ磷酸化位点和2个可能的PKC磷酸化位点；成功地克隆了s-lap蛋白编码区序列，构建了其真核表达载体，荧光显微镜观察，在转染pcDNA3．1-GFP质粒的B16黑色素瘤细胞中，荧光呈网状分布于细胞浆内，而细胞核内低表达；在转染s-lap／GFP融合基因的B16黑色素瘤细胞中，荧光均匀分布于整个细胞，尤其以细胞核内高表达。结论 新基因s-lap编码的蛋白质可在B16黑色素瘤细胞中获得表达，并以细胞核内高表达。     

钩端螺旋体基因组大小的初步研究

作者采用脉冲场凝胶电泳技术,对不同属、群(型)的5株钩端螺旋体基因组DNA分子量进行了研究,并用限制性内切酶Not I对基因组DNA进行分析。结果表明:钩端螺旋体基因组大小为2000kb;各株钩体基因组大小无明显差异;限制性内切酶Not I可将钩体基因组消化为11个大片段;钩体基因组DNA被Not I消化后电泳图谱与细菌基因组DNA图谱有很大差异。     

Health supervision for children with achondroplasia

Achondroplasia is the most common condition associated with disproportionate short stature. Substantial information is available concerning the natural history and anticipatory health supervision needs in children with this dwarfing disorder. Most children with achondroplasia have delayed motor milestones, problems with persistent or recurrent middle-ear dysfunction, and bowing of the lower legs. Less often, infants and children may have serious health consequences related to hydrocephalus, craniocervical junction compression, upper-airway obstruction, or thoracolumbar kyphosis. Anticipatory care should be directed at identifying children who are at high risk and intervening to prevent serious sequelae. This report is designed to help the pediatrician care for children with achondroplasia and their families.     

Prenatal screening and diagnosis for pediatricians

The pediatrician who cares for a child with a birth defect or genetic disorder may be in the best position to alert the family to the possibility of a recurrence of the same or similar problems in future offspring. The family may wish to know about and may benefit from methods that convert probability statements about recurrence risks into more precise knowledge about a specific abnormality in the fetus. The pediatrician also may be called on to discuss abnormal prenatal test results as a way of understanding the risks and complications that the newborn infant may face. Along with the increase in knowledge brought about by the sequencing of the human genome, there has been an increase in the technical capabilities for diagnosing many chromosome abnormalities, genetic disorders, and isolated birth defects in the prenatal period. The purpose of this report is to update the pediatrician about indications for prenatal diagnosis, current techniques used for prenatal diagnosis, and the status of maternal screenings for detection of fetal abnormalities.