权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Genetic Basis of Oligozoospermia in Infertile Males

不育男性少精症的遗传基础

基本信息

批准号：
8659195
负责人：
Alexander N Yatsenko
金额：
$ 12.57万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-06 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8659195
关键词：
Ablation Accounting Affect Apoptosis Biological Biological Assay Biopsy Breeding Candidate Disease Gene Categories Cell Proliferation Certification Characteristics Chromosome abnormality Chromosomes Clinical Collection Complementary DNA Contraceptive Agents Cytogenetic Analysis DNA DNA Sequence Data Defect Development Diagnosis Diagnostic Procedure Disease Environment Etiology Event Exons Fertility Fertilization Fluorescent in Situ Hybridization Gene Mutation Gene Order Genes Genetic Genetic Programming Genomic DNA Genomics Germ Cells Germ Lines Goals Haploidy Hereditary Disease Heterogeneity Human In Vitro Individual Infertility Investigation Knock-in Mouse Knock-out Knockout Mice Laboratories Lead Male Genital Organs Male Infertility Maps Medicine Methods Microarray Analysis Modeling Molecular Molecular Genetics Morphology Mus Mutant Strains Mice Mutate Mutation Nature Oligonucleotides Outcome Study Pathway interactions Patients Pattern Phenotype Physicians Physiological Physiology Point Mutation Proteins Protocols documentation RNA RNA Splicing Reporting Reproductive Biology Reproductive Health Reproductive Medicine Research Research Design Research Proposals Resolution Risk Sampling Scientist Seminal fluid Single-Gene Defect Sperm Count Procedure Sperm Maturation Spermatogenesis Staging Structure Technology Testing Testis Training Transgenic Mice Urology Work base career case control cell motility cohort college comparative genomic hybridization cost effective genetic analysis genetic linkage analysis genetic pedigree genome-wide human male in vivo insight male men mouse model mutant mouse model new technology novel novel diagnostics novel strategies offspring outcome forecast prevent reproductive screening spatiotemporal sperm cell

项目摘要

DESCRIPTION (provided by applicant): The applicant is a clinical molecular geneticist who is eligible for ABMG-accredited certification in the Clinical Molecular Genetics program. His long-term objective is to become an independent physician- scientist focused on studying the genetic bases of male infertility that affects the reproductive health of men. This proposal will provide the applicant with training in reproductive biology and new technologies in human and mouse genetics. The overall scientific goal of this project is to identify and characterize mutations in male infertility- associated genes that result in oligozoospermia (OS). Male infertility affects nearly 4,000,000 men in the USA, of which at least 25% are diagnosed as idiopathic. An etiology of male infertility is often associated with abnormal semen characteristics (i.e., sperm concentration, motility, morphology, etc.). Oligozoospermia is the most common semen abnormality observed among infertile males. The Specific Aims of the proposed study are: 1) Develop cDNA and DNA collections of oligozoospermic semen samples; 2) Study candidate genes for OS-associated mutations by direct cDNA sequencing and in vitro functional assays; 3) Identify and map genomic aberrations associated with severe OS, using oligo microarray comparative genome hybridization (CGH) technology; and 4) Characterize the CGH-detected gene-candidate that is associated with OS, using mouse knockout or knock-in models. The selection of OS-associated candidate genes will be prioritized according to their protein functional evidence and the gene's position in altered chromosome region. The applicant will study mutations and genomic abnormalities in cDNA and DNA samples from oligozoospermic patients, using cDNA sequencing approach and comprehensive genome-wide CGH microarray. A mutant mouse model will be developed in attempt to mimic the most common form of semen abnormality, oligozoospermia in human. The candidate will characterize the mutant mice by determining the spatiotemporal effects of gene ablation on spermatogenesis and fertilization. Identification and characterization specific gene mutations that associate with oligozoospermia will lead to the development of novel diagnostic procedures, and will help with prognosis in assisted reproductive medicine. Ultimately, it will provide insight into the molecular basis of male infertility, and eventually may facilitate the creation of non-hormonal contraceptives. Proposed study will be performed in an environment known for its collaborative studies in human and mouse genetics. The long-term career goals of the applicant is to become an independent physician-scientist focused on studying genetic disorders that affect male reproductive system.

描述（由申请人提供）：申请人是一名临床分子遗传学家，有资格获得ABMG认可的临床分子遗传学项目认证。他的长期目标是成为一名独立的医生-科学家，专注于研究影响男性生殖健康的男性不育症的遗传基础。该提案将为申请人提供生殖生物学和人类和小鼠遗传学新技术方面的培训。该项目的总体科学目标是识别和表征导致少精子症（OS）的男性不育相关基因突变。在美国，男性不育症影响近4，000，000名男性，其中至少25%被诊断为特发性。男性不育症的病因通常与异常精液特征（即，精子浓度、活力、形态等）。少精子症是不育男性中最常见的精液异常。本研究的具体目的是：1）建立少精子症精液标本的cDNA和DNA库; 2）通过直接cDNA测序和体外功能分析研究OS相关突变的候选基因; 3）利用寡核苷酸微阵列比较基因组杂交（CGH）技术鉴定和定位与严重OS相关的基因组畸变;和4）使用小鼠敲除或敲入模型表征CGH检测的与OS相关的候选基因。OS相关候选基因的选择将根据其蛋白质功能证据和基因在改变的染色体区域中的位置来优先考虑。申请人将使用cDNA测序方法和全面的全基因组CGH微阵列研究少精子症患者的cDNA和DNA样本中的突变和基因组异常。将开发一种突变小鼠模型，试图模拟人类最常见的精液异常形式，即少精子症。候选人将通过确定基因消融对精子发生和受精的时空影响来表征突变小鼠。鉴定和表征与少精子症相关的特定基因突变将导致新的诊断程序的发展，并将有助于辅助生殖医学的预后。最终，它将提供对男性不育的分子基础的深入了解，并最终可能促进非激素避孕药的创造。拟定研究将在以人类和小鼠遗传学合作研究而闻名的环境中进行。申请人的长期职业目标是成为一名独立的医生-科学家，专注于研究影响男性生殖系统的遗传疾病。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men.

DOI：
10.1056/nejmoa1406192
发表时间：
2015-05-28
期刊：
The New England journal of medicine
影响因子：
0
作者：
Yatsenko AN;Georgiadis AP;Röpke A;Berman AJ;Jaffe T;Olszewska M;Westernströer B;Sanfilippo J;Kurpisz M;Rajkovic A;Yatsenko SA;Kliesch S;Schlatt S;Tüttelmann F
通讯作者：
Tüttelmann F

Cytogenetic and molecular analyses of de novo translocation dic(9;13)(p11.2;p12) in an infertile male.

DOI：
10.1186/1755-8166-7-14
发表时间：
2014-02-21
期刊：
Molecular cytogenetics
影响因子：
1.3
作者：
Wiland E;Olszewska M;Georgiadis A;Huleyuk N;Panasiuk B;Zastavna D;Yatsenko SA;Jedrzejczak P;Midro AT;Yatsenko AN;Kurpisz M
通讯作者：
Kurpisz M

ETV5 mutations: revisiting Sertoli cell only syndrome.

ETV5 突变：重温仅支持细胞综合征。

DOI：
10.1016/j.fertnstert.2012.06.047
发表时间：
2012
期刊：
Fertility and sterility
影响因子：
6.7
作者：
Yatsenko,AlexanderN
通讯作者：
Yatsenko,AlexanderN

FISH and array CGH characterization of de novo derivative Y chromosome (Yq duplication and partial Yp deletion) in an azoospermic male.

无精男性中从头衍生 Y 染色体（Yq 重复和部分 Yp 缺失）的 FISH 和阵列 CGH 表征。

DOI：
10.1016/j.rbmo.2015.04.014
发表时间：
2015
期刊：
Reproductive biomedicine online
影响因子：
4
作者：
Wiland,Ewa;Yatsenko,AlexanderN;Kishore,Archana;Stanczak,Halina;Zdarta,Agata;Ligaj,Marcin;Olszewska,Marta;Wolski,JanKarol;Kurpisz,Maciej
通讯作者：
Kurpisz,Maciej

Familial Infertility (Azoospermia and Cryptozoospermia) in Two Brothers-Carriers of t(1;7) Complex Chromosomal Rearrangement (CCR): Molecular Cytogenetic Analysis.

t(1;7) 复杂染色体重排 (CCR) 两兄弟携带者的家族性不孕症（无精症和隐精症）：分子细胞遗传学分析。

DOI：
10.3390/ijms21124559
发表时间：
2020
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Olszewska,Marta;Stokowy,Tomasz;Pollock,Nijole;Huleyuk,Nataliya;Georgiadis,Andrew;Yatsenko,Svetlana;Zastavna,Danuta;Yatsenko,AlexanderN;Kurpisz,Maciej
通讯作者：
Kurpisz,Maciej