Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific ...Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .展开更多
The V-MYC avian myelocytomatosis viral-related onco- gene, a neuroblastoma-derived gene （MYCN, MIM： 164840） located on chromosome 2p24, was previously found to be associated with Feingold syndrome 1 （FGLDS1, MIM：...The V-MYC avian myelocytomatosis viral-related onco- gene, a neuroblastoma-derived gene （MYCN, MIM： 164840） located on chromosome 2p24, was previously found to be associated with Feingold syndrome 1 （FGLDS1, MIM： 164280） [1]. FGLDS1 is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disabilities. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients [2]. Despite the involvement of intellectual disability in FGLDS1, the molecular mechanisms of the MYCN gene in regulating brain development remain largely unclear.Some truncated mutations in the N terminus of the MYCN have been identified in FGLDS1 [1, 3].展开更多
目的探讨染色体微阵列分析技术(CMA)在检查核型分析未见异常的发育迟缓/智力低下(DD/ID)患儿方面的应用价值。方法选取210例DD/ID伴或不伴其他异常患儿,分为2组:单纯性DD/ID组( n =90),复杂性DD/ID组( n =120例,合并癫痫23例、头颅磁共...目的探讨染色体微阵列分析技术(CMA)在检查核型分析未见异常的发育迟缓/智力低下(DD/ID)患儿方面的应用价值。方法选取210例DD/ID伴或不伴其他异常患儿,分为2组:单纯性DD/ID组( n =90),复杂性DD/ID组( n =120例,合并癫痫23例、头颅磁共振异常36例、心血管系统19例、多发结构畸形42例)。提取其外周血DNA,采用CGXv1.18-plex基因芯片进行全基因组拷贝数变异(CNVs)检测,查询国际病理性CNV数据库(ClinVar、DECIPHER、OMIM等)、DGV数据库,检索PubMed数据库相关文献,对CNVs致病性进行分析。结果在210例DD/ID患儿中检出83例染色体拷贝数异常,检出率为39.5%。其中,检出已知致病的常见微缺失/微重复综合征66例;罕见综合征1例(Kleefstra综合征)。可疑致病变异的微缺失/微重复9例,可能良性变异1例,临床意义不明6例。结论 CMA可以明显提高DD/ID患儿遗传学病因的诊断率,对于患儿的治疗及其父母的再生育具有重要的指导意义。因此可以作为DD/ID患儿的一线诊断方法。展开更多
文摘Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .
基金supported by grants from the National Natural Science Foundation of China(81701494)the Shanghai Municipal Commission of Health and Family Planning(2013ZYJB0015)the Science and Technology Commission of Shanghai Municipality(14411950402)
文摘The V-MYC avian myelocytomatosis viral-related onco- gene, a neuroblastoma-derived gene （MYCN, MIM： 164840） located on chromosome 2p24, was previously found to be associated with Feingold syndrome 1 （FGLDS1, MIM： 164280） [1]. FGLDS1 is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disabilities. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients [2]. Despite the involvement of intellectual disability in FGLDS1, the molecular mechanisms of the MYCN gene in regulating brain development remain largely unclear.Some truncated mutations in the N terminus of the MYCN have been identified in FGLDS1 [1, 3].
文摘目的探讨染色体微阵列分析技术(CMA)在检查核型分析未见异常的发育迟缓/智力低下(DD/ID)患儿方面的应用价值。方法选取210例DD/ID伴或不伴其他异常患儿,分为2组:单纯性DD/ID组( n =90),复杂性DD/ID组( n =120例,合并癫痫23例、头颅磁共振异常36例、心血管系统19例、多发结构畸形42例)。提取其外周血DNA,采用CGXv1.18-plex基因芯片进行全基因组拷贝数变异(CNVs)检测,查询国际病理性CNV数据库(ClinVar、DECIPHER、OMIM等)、DGV数据库,检索PubMed数据库相关文献,对CNVs致病性进行分析。结果在210例DD/ID患儿中检出83例染色体拷贝数异常,检出率为39.5%。其中,检出已知致病的常见微缺失/微重复综合征66例;罕见综合征1例(Kleefstra综合征)。可疑致病变异的微缺失/微重复9例,可能良性变异1例,临床意义不明6例。结论 CMA可以明显提高DD/ID患儿遗传学病因的诊断率,对于患儿的治疗及其父母的再生育具有重要的指导意义。因此可以作为DD/ID患儿的一线诊断方法。
