Genetic analysis of neonatal growth retardation, a lethal syndrome with multiple genes involving X-and Y-linked ones

新生儿生长迟缓的遗传分析，这是一种涉及 X 和 Y 连锁多基因的致命综合征

• 批准号: 15500305
• 负责人: SUTO Jun-ichi
• 金额: $ 1.98万
• 依托单位: National Institute of Agrobiological Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500305/
• 关键词: Dh (Dominant hemimelia); growth retardation; neonatal lethality; Multigenic trait; X chromosome; Y chromosome; Y consomic strains; testis weight; 致死症; Y染色体コンソミックマウス; DDD; 新生仔成長傷害・致死; X染色体(Grdhq1); 多因子性疾患

Most F_1-Dh/+ males, crosses between inbred DDD strain females and DH-Dh/+ strain males, die during the neonatal period. Affected F_1-Dh/+ males exhibit a typical symptom of growth retardation, with problems of urination and defecation. This is caused by a rectovesical fistula formed between the rectum and the urinary bladder in conjunction with an imperforate anus. The lethal phenotype does not occur in the reciprocal cross between DH-Dh/+ females and DDD males. Genetic mapping analysis of the loci underlying the lethality has revealed that the lethality is a consequence of synergism among three independent gene loci; that is, the DH allele at Dh locus on Chr 1, the DDD allele at the Grdhq1 locus on the X Chr, and a putative Y-linked locus in some inbred strains. By establishing Y chromosome consomic strains, I proved the commitment of Y-linked gene(s). During the course of the study, I noticed that Dh has effects on male fertility, and obtained some preliminary results that Dh may interacts with more than one Y-linked genes.

大多数 F_1-Dh/+ 雄性（近交 DDD 品系雌性与 DH-Dh/+ 品系雄性之间杂交）在新生儿期死亡。受影响的F_1-Dh/+雄性表现出典型的生长迟缓症状，并伴有排尿和排便问题。这是由直肠和膀胱之间形成的直肠膀胱瘘以及肛门闭锁引起的。致死表型不会出现在 DH-Dh/+ 雌性和 DDD 雄性之间的互交中。对致死性基因座的遗传图谱分析表明，致死性是三个独立基因座之间协同作用的结果；也就是说，Chr 1 上 Dh 基因座的 DH 等位基因、X Chr 上 Grdhq1 基因座的 DDD 等位基因以及某些近交品系中推定的 Y 连锁基因座。通过建立Y染色体共体株，我证明了Y连锁基因的承诺。在研究过程中，我注意到Dh对男性生育能力有影响，并得到了一些初步结果，Dh可能与多个Y连锁基因相互作用。