IDENTIFICATION OF IMPRINTED GENES ON CHROMOSOME 14

单亲二体（UPD）是来自同一亲本的染色体的两个副本的异常遗传，而没有来自另一个亲本的特定染色体的贡献。UPD已被描述为许多人类染色体，导致不同的临床结果。异常表型可能是由于染色体上的基因受到基因组印记的影响。基因组印记是一种分子机制，通过这种机制，来自母系或父系遗传染色体的基因可以有不同的表达。临床描述的情况下，无论是母亲和父亲二体14已使不同的综合征的特征为每一个。患有父亲畸形14的个体表现出多种表型，包括智力低下，骨骼异常导致短肢侏儒症和狭窄的胸腔，由于呼吸困难，畸形相，脊柱侧凸和身材矮小而降低生存率。本应用程序提出通过两个特定目的来识别人类14号染色体上的印迹基因。首先，将从母系和父系染色体中鉴定出差异表达序列14。来自母体14二体或父亲14二体细胞系的表达序列将通过直接分析已知基因、与阵列cDNA过滤器杂交和抑制减法杂交来鉴定印迹基因进行比较。其次，对差异表达序列进行表征，以了解基因组印迹的分子机制和表型的影响。将对差异表达序列进行测序，并鉴定全长cdna。序列将被分析为亲本特异性甲基化和表达，以开始了解用于控制印迹过程的分子元件。基因组印迹基因的鉴定将有助于深入了解基因组印迹在正常和异常人类发育和智力迟钝综合征中的作用机制，并可能进一步推动UPD疾病的诊断和分子理解。

Uniparental disomy (UPD) is the abnormal inheritance of both copies of chromosome from the same parent with no contribution of that particular chromosome from the other parent. UPD has been described for many human chromosomes, resulting in varying clinical outcomes. An abnormal phenotype may result from genes on a chromosome that are subject to genomic imprinting. Genomic imprinting is the molecular mechanism by which there can be differential expression of genes from either the maternally-or paternally inherited chromosome. The clinical description of cases with either maternal and paternal disomy 14 has enable the characterization of distinct syndromes for each. Individuals with paternal disomy 14 present with a more several phenotype with includes mental retardation, skeletal abnormalities that result in a short- limb dwarfism with narrow thorax, decreased survival due to respiratory difficulties, dysmorphic facies, scoliosis, and short status. This application proposes to identify imprinted genes on human chromosome 14 through two Specific Aims. First, differentially expressed sequences will be identified from maternally- and paternally-derived chromosomes 14. Expressed sequences from cell lines of either maternal disomy 14 or paternal disomy 14 will be compared through direct analysis of known genes, hybridization to arrayed cDNA filters, and suppression subtraction hybridization to identify imprinted genes. Second, differentially expressed sequences will be characterized in order to understand the molecular mechanism of genomic imprinting and the effects of phenotype. The differentially expressed sequences will be sequenced and full length cDNAs will be identified. Sequences will be analyzed for parent-specific methylation and expression to begin to understand the molecular elements used to control the imprinting process. The identification of genes that are subject to genomic imprinting will allow insight into the mechanisms of genomic imprinting in normal and abnormal human development and mental retardation syndromes and may lead to further advances in the diagnosis and molecular understanding of UPD disorders.