大Y染色體臨床效應(yīng)及其形成機(jī)理初步研究
發(fā)布時(shí)間：2018-07-21 10:16
【摘要】： 染色體多態(tài)性是指人類群體中染色體形態(tài)存在的微小差異。傳統(tǒng)的遺傳學(xué)認(rèn)為,染色體多態(tài)性通常不具有明顯的表型或病理學(xué)意義。但越來(lái)越多的研究表明,染色體多態(tài)性可產(chǎn)生臨床效應(yīng),與生殖異常有關(guān),包括早期復(fù)發(fā)性自然流產(chǎn)、早期胚胎停止發(fā)育、胎兒畸形等。 大Y染色體是常見(jiàn)的染色體多態(tài)性。據(jù)統(tǒng)計(jì),大Y染色體在生殖異常的男性患者中的比例達(dá)2.18%-21.73%。隨著生殖輔助技術(shù)的日益發(fā)展,許多不孕不育的患者求助于體外受精-胚胎移植技術(shù),其中不乏有大Y患者。 關(guān)于大Y的形成機(jī)理的研究較少。Yassmine對(duì)一例胎兒的產(chǎn)前診斷及出生后診斷均為Yqh+／Yqh-嵌合體,推測(cè)這種情況可能是來(lái)源于合子形成后DYZ區(qū)的缺失或者姐妹染色單體的不平等交換。由此推測(cè)大Y的形成可能與DYZ區(qū)相關(guān)。 DYZ(human Y-chromosome specific repeated DNA family)是指人類Y染色體上特異性的重復(fù)序列,現(xiàn)在已經(jīng)確定的包括DYZ1、DYZ2和DYZ3。其中DYZ1是Y染色體長(zhǎng)臂遠(yuǎn)端的異染色質(zhì)中主要串聯(lián)重復(fù)序列,占Y染色體總長(zhǎng)度的約40%。DYZ1長(zhǎng)度為3.6kb,2000-4000次為其在正常男性人類的重復(fù)次數(shù)。 Deepali等將暴露于射線的男性與復(fù)發(fā)性自然流產(chǎn)(Recurrent spontaneousabortion, RSA)患者丈夫的DYZ1穩(wěn)定性進(jìn)行比較,發(fā)現(xiàn)后者的不穩(wěn)定性更加常見(jiàn),推測(cè)DYZ1在Y染色體的折疊和結(jié)構(gòu)完整性方面有關(guān)鍵作用。 基于以上研究背景,本研究首先通過(guò)回顧性臨床研究來(lái)探討大Y染色體對(duì)體外受精-胚胎移植結(jié)局的影響。然后,通過(guò)對(duì)Y染色體上DYZ1完整性及拷貝數(shù)檢測(cè)研究其在Y染色體多態(tài)性患者和早期復(fù)發(fā)性流產(chǎn)患者丈夫中的變化,以期探討DYZ1在Y染色體多態(tài)性和早期復(fù)發(fā)性流產(chǎn)所起的作用。 第一部分：大Y染色體對(duì)體外受精-胚胎移植結(jié)局的影響 【目的】通過(guò)回顧性研究探討大Y染色體對(duì)體外受精-胚胎移植結(jié)局的影響。 【方法】選取2006年1月至2008年12月在山東大學(xué)附屬省立醫(yī)院生殖醫(yī)學(xué)中心完成的體外受精.新鮮胚胎移植周期。其中,男方染色體G顯帶為大Y(Y≥18號(hào)染色體)且其妻排除已知的影響體外受精.胚胎移植結(jié)果的疾病的治療周期為大Y組(33例患者,47個(gè)治療周期),同期在本中心進(jìn)行體外受精-鮮胚移植治療的其他治療周期為群體對(duì)照組(共6620個(gè)治療周期)。 【結(jié)果】大Y組與群體對(duì)照組比較,其受精率、卵裂率、優(yōu)質(zhì)胚胎率、種植率、妊娠率、早期流產(chǎn)率等各項(xiàng)指標(biāo)的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),但在畸形率、出生性別比例方面,兩組比較差異具有統(tǒng)計(jì)學(xué)意義(P0.05),即大Y組畸形兒出生與出生女孩所占比例有明顯升高。 【結(jié)論】大Y染色體對(duì)體外受精-胚胎移植的胚胎發(fā)育及近期妊娠結(jié)果均無(wú)顯著性影響,但在大Y染色體患者的妻子行體外受精-胚胎移植時(shí),女孩更易出生。 第二部分：DYZ1穩(wěn)定性在Y染色體多態(tài)性和早期復(fù)發(fā)性流產(chǎn)中的研究 【目的】通過(guò)對(duì)DYZ1完整性及拷貝數(shù)檢測(cè),探討DYZ1在Y染色體多態(tài)性和早期復(fù)發(fā)性流產(chǎn)中所起的作用。 【方法】對(duì)同期就診于本中心的男性的DYZ1進(jìn)行研究。其中,不明原因早期RSA患者丈夫106例；Y染色體多態(tài)性患者86例,包括大Y患者(Y≥18號(hào)染色體)79例和小Y患者(Y≤21號(hào)染色體)7例,同期就診的已正常生育并排除染色體異常的男性100例。 【結(jié)果】通過(guò)PCR電泳,在RSA患者丈夫中1例存在DYZ1頭部的266個(gè)堿基(第25-290個(gè)堿基)缺失,2例存在DYZ1中部的773個(gè)堿基缺失(第1347-2119堿基)；在小Y患者中2例存在DYZ1頭部的266個(gè)堿基(第25-290個(gè)堿基)缺失,4例存在中部的773個(gè)堿基缺失(第1347-2119堿基)和尾部的275個(gè)基因缺失(第3128-3420堿基)；在大Y患者和正常生育者中未發(fā)現(xiàn)DYZ1部分缺失。通過(guò)實(shí)時(shí)熒光定量PCR,正常生育男性的DYZ1拷貝數(shù)平均為3900；大Y患者的平均值為5571,與正常生育者比較差異有統(tǒng)計(jì)學(xué)意義(P0.007),即大Y患者DYZ1拷貝數(shù)比正常生育男性多；小Y患者的平均值為1059,與正常生育者比較差異有統(tǒng)計(jì)學(xué)意義(P0.001),即小Y患者DYZ1拷貝數(shù)比正常生育男性少；RSA患者丈夫的平均值為2655,與正常生育者比較差異有統(tǒng)計(jì)學(xué)意義(P0.001),即RSA患者丈夫DYZ1拷貝數(shù)比正常生育男性少。 【結(jié)論】DYZ1拷貝數(shù)增多可使顯微鏡下可視的Y染色體長(zhǎng)度增加；DYZ1部分缺失和拷貝數(shù)減少可使顯微鏡下可視的Y染色體長(zhǎng)度減少；DYZ1拷貝數(shù)正常范圍內(nèi)顯著減少可能是早期復(fù)發(fā)性自然流產(chǎn)的病因之一。
[Abstract]:Chromosome polymorphism is a small difference in the form of chromosomes in a human population. Traditional genetics believes that chromosome polymorphism does not usually have obvious phenotypic or pathological significance. However, more and more studies have shown that chromosome polymorphisms can produce clinical effects, related to reproductive abnormalities, including early recurrent spontaneous abortion, early recurrent spontaneous abortion. The embryonic development, fetal malformation, and so on.
The large Y chromosome is a common chromosome polymorphism. According to statistics, the proportion of large Y chromosomes in male patients with reproductive abnormalities is 2.18%-21.73%., with the growing development of reproductive technology, many infertile patients have turned to in vitro fertilization and embryo transfer technology, among which there are no lack of large Y patients.
The study of the formation mechanism of large Y is less than.Yassmine for prenatal diagnosis and postnatal diagnosis of a fetus with Yqh+ / Yqh- chimerism. It is presumed that this situation may be derived from the deletion of the DYZ region after the formation of the zygote or the unequal exchange of sister chromatid. Therefore, the formation of large Y may be related to the DYZ region.
DYZ (human Y-chromosome specific repeated DNA family) refers to the specific repeat sequence on the human Y chromosome, which is now identified as DYZ1, DYZ2, and DYZ3.. DYZ1 is the main tandem repeats in the heterochromatin on the distal end of the long arm of the chromosome, accounting for the length of the total length of the chromosomes, and the 2000-4000 time it is in the positive. The number of repetitions of men.
Deepali and other radiographic men were compared with the DYZ1 stability of the Recurrent spontaneousabortion (RSA) patients. It was found that the instability of the latter was more common. It was suggested that DYZ1 had a key role in the folding and structural integrity of the Y chromosome.
Based on the above research background, this study first explored the effect of the large Y chromosome on the outcome of in vitro fertilization and embryo transfer through a retrospective clinical study. Then, the changes in the DYZ1 integrity and copy number of the Y chromosomes in the Y chromosome polymorphisms and the early recurrent flow patients were examined in order to explore the DYZ1 in Y. The role of chromosomal polymorphism and early recurrent spontaneous abortion.
Part I: the effect of large Y chromosome on the outcome of IVF embryo transfer
[Objective] to investigate the effect of large Y chromosome on the outcome of IVF embryo transfer in a retrospective study.
[Methods] in vitro fertilization and fresh embryo transfer period from January 2006 to December 2008 at the reproductive medical center of the Provincial Hospital Affiliated to Shandong University. In which the male chromosome G showed a large Y (Y > 18) and the wife excluded the known effect of in vitro fertilization. The treatment cycle of the result of embryo transfer was a large group of Y (33 cases). Patients, 47 treatment cycles), and other treatment cycles in the same period in the center for in vitro fertilization and fresh embryo transfer were group control (a total of 6620 treatment cycles).
[results] there was no significant difference in fertilization rate, cleavage rate, high quality embryo rate, implant rate, pregnancy rate and early abortion rate, but there was no significant difference between the two groups (P0.05), but the difference between the two groups was statistically significant (P0.05) in the deformity rate and the birth sex ratio (P0.05), that is, the large Y group was born and the girl was born There was a significant increase in the proportion.
[Conclusion] there is no significant effect of the large Y chromosome on the embryo development and the recent pregnancy results of in vitro fertilization and embryo transfer, but the girl is more likely to be born when the wife of the large Y chromosome patient is in vitro fertilization and embryo transfer.
The second part: DYZ1 stability in Y chromosome polymorphism and early recurrent spontaneous abortion.
[Objective] to explore the role of DYZ1 in Y chromosome polymorphism and early recurrent spontaneous abortion by detecting the integrity and copy number of DYZ1.
[Methods] a study was conducted on the male DYZ1 in the center for the same period. Among them, 106 cases of unexplained early RSA were husbands and 86 cases of Y chromosome polymorphisms, including 79 cases of large Y (Y > 18 chromosome) and 7 cases of small Y patients (Y < 21 chromosome), and 100 men who had normal birth and excluded abnormal chromosomes during the same period.
[results] by PCR electrophoresis, 266 bases (25-290 base) of DYZ1 head were absent in 1 cases of RSA's husbands, 2 cases had 773 base deletion (1347-2119 base) in central DYZ1; 2 cases in small Y patients had 266 bases (25-290 base) deletion in the head and 4 cases of deletion of Central RSA base (1347-). 2119 base and 275 gene deletion (3128-3420 base) in the tail; no partial deletion of DYZ1 was found in patients with large Y and normal fertility. By real-time fluorescence quantitative PCR, the average DYZ1 copy number of normal fertile men was 3900; the average value of the large Y patients was 5571, and the difference was statistically significant (P0.007), that is, large Y patients (P0.007). The number of copies of DYZ1 was more than that of the normal male, and the average value of the small Y patients was 1059, and the difference was statistically significant (P0.001), that is, the DYZ1 copies of the small Y patients were less than those of the normal ones; the mean value of the husbands of the RSA patients was 2655, and the difference was statistically significant (P0.001), that is, the husband DYZ1 of the RSA patient. The number of copies is less than that of normal fertile men.
[Conclusion] the increase of DYZ1 copy number can increase the length of Y chromosome visible under the microscope, and the deletion of DYZ1 and the decrease of copy number can reduce the length of the visible Y chromosome under the microscope, and the significant decrease in the normal range of DYZ1 copy number may be one of the causes of the early recurrent spontaneous abortion.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R394
本文編號(hào)：2135201
[Abstract]:Chromosome polymorphism is a small difference in the form of chromosomes in a human population. Traditional genetics believes that chromosome polymorphism does not usually have obvious phenotypic or pathological significance. However, more and more studies have shown that chromosome polymorphisms can produce clinical effects, related to reproductive abnormalities, including early recurrent spontaneous abortion, early recurrent spontaneous abortion. The embryonic development, fetal malformation, and so on.
The large Y chromosome is a common chromosome polymorphism. According to statistics, the proportion of large Y chromosomes in male patients with reproductive abnormalities is 2.18%-21.73%., with the growing development of reproductive technology, many infertile patients have turned to in vitro fertilization and embryo transfer technology, among which there are no lack of large Y patients.
The study of the formation mechanism of large Y is less than.Yassmine for prenatal diagnosis and postnatal diagnosis of a fetus with Yqh+ / Yqh- chimerism. It is presumed that this situation may be derived from the deletion of the DYZ region after the formation of the zygote or the unequal exchange of sister chromatid. Therefore, the formation of large Y may be related to the DYZ region.
DYZ (human Y-chromosome specific repeated DNA family) refers to the specific repeat sequence on the human Y chromosome, which is now identified as DYZ1, DYZ2, and DYZ3.. DYZ1 is the main tandem repeats in the heterochromatin on the distal end of the long arm of the chromosome, accounting for the length of the total length of the chromosomes, and the 2000-4000 time it is in the positive. The number of repetitions of men.
Deepali and other radiographic men were compared with the DYZ1 stability of the Recurrent spontaneousabortion (RSA) patients. It was found that the instability of the latter was more common. It was suggested that DYZ1 had a key role in the folding and structural integrity of the Y chromosome.
Based on the above research background, this study first explored the effect of the large Y chromosome on the outcome of in vitro fertilization and embryo transfer through a retrospective clinical study. Then, the changes in the DYZ1 integrity and copy number of the Y chromosomes in the Y chromosome polymorphisms and the early recurrent flow patients were examined in order to explore the DYZ1 in Y. The role of chromosomal polymorphism and early recurrent spontaneous abortion.
Part I: the effect of large Y chromosome on the outcome of IVF embryo transfer
[Objective] to investigate the effect of large Y chromosome on the outcome of IVF embryo transfer in a retrospective study.
[Methods] in vitro fertilization and fresh embryo transfer period from January 2006 to December 2008 at the reproductive medical center of the Provincial Hospital Affiliated to Shandong University. In which the male chromosome G showed a large Y (Y > 18) and the wife excluded the known effect of in vitro fertilization. The treatment cycle of the result of embryo transfer was a large group of Y (33 cases). Patients, 47 treatment cycles), and other treatment cycles in the same period in the center for in vitro fertilization and fresh embryo transfer were group control (a total of 6620 treatment cycles).
[results] there was no significant difference in fertilization rate, cleavage rate, high quality embryo rate, implant rate, pregnancy rate and early abortion rate, but there was no significant difference between the two groups (P0.05), but the difference between the two groups was statistically significant (P0.05) in the deformity rate and the birth sex ratio (P0.05), that is, the large Y group was born and the girl was born There was a significant increase in the proportion.
[Conclusion] there is no significant effect of the large Y chromosome on the embryo development and the recent pregnancy results of in vitro fertilization and embryo transfer, but the girl is more likely to be born when the wife of the large Y chromosome patient is in vitro fertilization and embryo transfer.
The second part: DYZ1 stability in Y chromosome polymorphism and early recurrent spontaneous abortion.
[Objective] to explore the role of DYZ1 in Y chromosome polymorphism and early recurrent spontaneous abortion by detecting the integrity and copy number of DYZ1.
[Methods] a study was conducted on the male DYZ1 in the center for the same period. Among them, 106 cases of unexplained early RSA were husbands and 86 cases of Y chromosome polymorphisms, including 79 cases of large Y (Y > 18 chromosome) and 7 cases of small Y patients (Y < 21 chromosome), and 100 men who had normal birth and excluded abnormal chromosomes during the same period.
[results] by PCR electrophoresis, 266 bases (25-290 base) of DYZ1 head were absent in 1 cases of RSA's husbands, 2 cases had 773 base deletion (1347-2119 base) in central DYZ1; 2 cases in small Y patients had 266 bases (25-290 base) deletion in the head and 4 cases of deletion of Central RSA base (1347-). 2119 base and 275 gene deletion (3128-3420 base) in the tail; no partial deletion of DYZ1 was found in patients with large Y and normal fertility. By real-time fluorescence quantitative PCR, the average DYZ1 copy number of normal fertile men was 3900; the average value of the large Y patients was 5571, and the difference was statistically significant (P0.007), that is, large Y patients (P0.007). The number of copies of DYZ1 was more than that of the normal male, and the average value of the small Y patients was 1059, and the difference was statistically significant (P0.001), that is, the DYZ1 copies of the small Y patients were less than those of the normal ones; the mean value of the husbands of the RSA patients was 2655, and the difference was statistically significant (P0.001), that is, the husband DYZ1 of the RSA patient. The number of copies is less than that of normal fertile men.
[Conclusion] the increase of DYZ1 copy number can increase the length of Y chromosome visible under the microscope, and the deletion of DYZ1 and the decrease of copy number can reduce the length of the visible Y chromosome under the microscope, and the significant decrease in the normal range of DYZ1 copy number may be one of the causes of the early recurrent spontaneous abortion.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R394
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 朱運(yùn)良,伍新堯;Y染色體MSY區(qū)域內(nèi)DNA分子重組[J];國(guó)外醫(yī)學(xué).遺傳學(xué)分冊(cè);2004年05期
2 田二坡;秦達(dá)念;;Y染色體與男性不育關(guān)系的研究進(jìn)展[J];中華男科學(xué)雜志;2007年06期
3 李錚;陳向鋒;沙艷偉;;人類Y染色體進(jìn)化突變與男性不育[J];中華男科學(xué)雜志;2009年04期
4 王麗,許立紅,張浩波,房玉英,李曉,陳子江;通過(guò)輔助生殖技術(shù)出生的后代性別比例分析[J];山東醫(yī)藥;2005年24期
5 陳留存,王金星;異染色質(zhì)研究進(jìn)展[J];生物學(xué)通報(bào);1998年01期
6 胡曉東;曾勇;莫美蘭;林奇;蔡靖;郭楚蘋;鄧江林;;大Y染色體對(duì)體外受精與胚胎移植的影響[J];實(shí)用醫(yī)學(xué)雜志;2007年02期
7 楊軍;伍宗惠;;Y染色體異常的臨床表現(xiàn)與遺傳學(xué)相關(guān)分析[J];現(xiàn)代醫(yī)藥衛(wèi)生;2008年12期
8 Christopher J Haines;;"Micro-deletions" of the human Y chromosome and their relationship with male infertility[J];遺傳學(xué)報(bào);2008年04期
9 陳蔚清;;染色體多態(tài)性的臨床效應(yīng)[J];中國(guó)婦幼保健;2007年10期
10 劉志婷;王軍榮;潘雨利;魏振彤;;變異染色體引起生殖異常的臨床效應(yīng)[J];中國(guó)婦幼保健;2007年15期
，本文編號(hào)：2135201
本文鏈接：http://sikaile.net/yixuelunwen/shiyanyixue/2135201.html
最近更新
教材專著
