| Part?Recurrent Deletions of the X Chromosome Linked CNV64,CNV67,and CNV69 and male infertility in Chinese Han populationBackground and Objective: Copy number variations(CNVs)are a kind of chromosome structural variation.CNVs refer to a segment of DNA ranging from one kilobase to several megabases in size that represents an imbalance between two genomes from one species.Earlier CNVs were discovered to be responsible for a wide range of human diseases like neuro-developmental disorders,cardiac abnormalities,and other abnormalities.A recent study found that three recurrent deletions of X chromosome linked copy number variations(CNVs),CNV64,CNV67 and CNV69 were associated with idiopathic male infertility in Spanish and Italian populations,especially CNV67 resembling the azoospermia factor(AZF)deletions.That merits further investigations among different populations.Are the three X chromosome-linked recurrent deletions associated with the idiopathic male infertility in Chinese Han population? This study was conducted to examine the prevalence of the three CNVs and their associations with idiopathic male infertility in Chinese Han population.Method and Materials: Our study included a large population of 1550 Chinese Han subjects recruited between 2014 and 2016.In total,714 infertile participants were diagnosed as idiopathic infertility with different conditions(288 with non-obstructive azoospermia,210 oligozoospermia and 216 asthenospermia)and 836 fertile participants(vasectomized men).The fertile participants were recruited from the representative areas: the north China(Hebei and Shanxi),centre(Hubei and Jiangsu),and south(Guangdong).All patients were recruited from Hubei province.Plus/minus PCR was performed to detect and confirm the three CNVs.Result: In fertile group,CNV64 and CNV67 deletions were significantly different between the south China and other regions.The total CNV64 deletion rate was 3.71%(31/836)and 5.31% in north China(Beijing 5/94,Shanxi 8/151),4.96% in centre China(Hubei 12/241,Jiangsu 5/102),0.40% in south China(Guangdong 1/248).The rate of CNV64 deletion in Guangdong was significantly lower than in other regions(P=0.004),while its deletion in other four provinces was quite similar.CNV67 deletion rate in Guangdong population was about 3.23%,significantly higher than in other regions(P=0.01),of which only one case with the deletion was found in Shanxi population.Regarding CNV69,only one carrier was detected in Hubei province.CNV64 deletion rates in patients with NOA,oligozoospermia and asthenospermia were 4.86%,5.24%,and 5.56% respectively.The prevalent rates were similar to the fertile men originated from central China(4.96%).Considering that infertile subjects were recruited from Hubei,a more strict comparison between the different conditions of infertile men and fertile men originated from the same region showed no significant difference.Overall,CNV69 was rare in different conditions of infertile men and fertile men(one carrier in NOA group,one carrier in fertile group).CNV67 was also scare,and only two carriers were observed in 714 patients(one in oligozoospermia and one in asthenospermia).Conclusions: No association between the three CNVs deletions and idiopathic male infertility was observed.And CNV67 is rare in centre China,albeit large sample size study for confirmation is warranted.It seems that the association between these CNVs and idiopathic male infertility is ethnic dependent.Part? X chromosome linked genes Exon Mutation in Non-obstructive Azoospermia of Chinese Han PopulationBackground and objective: Non-obstructive azoospermia(NOA)is the most serious kind of male infertility.Genetic factors are supposed to be the main cause of NOA.However,the known genetic causes of NOA are chromosomal abnormalities and Y chromosome microdeletions(AZF),only accounting for 25% etiology of them.The pathogenic basis of NOA is the failure of spermatogenesis.Many genes affect the process of spermatogenesis.Aiming to identify the genes that can be applied in the diagnosis of genetic abnormalities of NOA and to provide genetic counseling for patients with NOA,this study conducted the target gene capture sequencing technology to screen the single nucleotide mutations of 22 X chromosome linked genes with potential role in spermatogenesis of mammal.Method and Materials: Case group included 776 Chinese Han males recruited from Wuhan Tongji Reproductive Hospital between 2007 and 2011.They were diagnosed as nonobstructive azoospermia,aged between 24 and 46 years,with an average age of 30.6 years.Diagnostic criteria:(1)semen routine examination of three times without sperm;(2)rule out infertility caused by known factors such as obstruction factors,reproductive system inflammatory or trauma;(3)without Y chromosome microdeletion,without karyotype abnormalities.The control group included 709 heathly Chinese Han men recruited from Peking University,Shenzhen Hospital,aged between 29-51 years old,with an average age of 35.6 years.In this study,22 genes(Most of the genes were associated with spermatogenesis by mouse gene knockout models)on the X chromosome were selected reference to Pubmed,OMIM,MGI and other databases(some genes were associated with spermatogenesis in mouse knockout model).The genomic DNA of peripheral blood was extracted from 1485 subjects,and the genomic library was established.Then target sequencing and bioinformatics analysis were performed.Result: A total of 92 functional mutations were found in 776 NOA patients,and a total of 86 functional mutations were found in 709 controls.KAL1,NR0B1,AKAP4,TEX11,USP26,and NR0B1 gene functional mutations were found relatively more frequency in patients with NOA.NR0B1 functional mutation occurred only in patients with significant difference.KAL1 functional mutations were only seen in patients;however,it did not achieve statistical significance.Conclusions: X chromosome linked genes KAL1,NR0B1,AKAP4,TEX11,USP26 may be the target gene of NOA Etiology study... |
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