造血系统嵌合型Y染色体丢失：从人群队列到致病机制

doi:10.16288/j.yczz.24-211

遗传 ›› 2025, Vol. 47 ›› Issue (4): 409-427.doi: 10.16288/j.yczz.24-211

造血系统嵌合型Y染色体丢失：从人群队列到致病机制

朱丽娜¹(), 汪旭¹^,², 郭锡汉¹()

1.云南师范大学生命科学学院，昆明 650500
2.台州耶大基因与细胞治疗研究院，台州 318000

收稿日期:2024-07-17 修回日期:2024-09-24 出版日期:2025-04-20 发布日期:2024-09-26
通讯作者: 郭锡汉，博士，副教授，研究方向：Y染色体丢失的病理生理学效应。E-mail: guo_xihan@163.com
作者简介:朱丽娜，硕士研究生，专业方向：Y染色体丢失与阿尔茨海默病。E-mail: 3117698437@qq.com
基金资助:
国家自然科学基金项目(32260148);国家自然科学基金项目(31900410);云南省兴滇英才-青年人才项目资助

Hematopoietic mosaic loss of Y chromosome: from population cohorts to pathogenic mechanisms

Lina Zhu¹(), Xu Wang¹^,², Xihan Guo¹()

1. School of Life Sciences, Yunnan Normal University, Kunming 650500, China
2. Yeda Institute of Gene and Cell Therapy, Taizhou 318000, China

Received:2024-07-17 Revised:2024-09-24 Published:2025-04-20 Online:2024-09-26
Supported by:
National Natural Science Foundation of China(32260148);National Natural Science Foundation of China(31900410);Xing Dian Plan “Youth Talent Program” of Yunnan Province

摘要/Abstract

摘要：

嵌合型Y染色体丢失(mosaic loss of Y chromosome (LOY), mLOY)是指男性部分体细胞因Y染色体(Y chromosome, ChrY)丢失而与非LOY细胞形成的遗传嵌合现象。mLOY主要发现于血液中，不仅因为血细胞易取样，更因为发生LOY突变的造血干细胞在获得竞争优势后可驱动克隆性造血，产生大量携带LOY突变的血细胞。由于结构的特殊性，人ChrY在有丝分裂时易发生异常分离，同时在种系突变、环境暴露、衰老微环境等因素的驱动下，mLOY成为男性体细胞中最常见的获得性突变。早期的人群队列研究显示造血系统mLOY与男性预期寿命缩短以及癌症、阿尔茨海默病和心血管疾病等慢病风险增加显著相关，近期的小鼠模型研究表明mLOY是白血病和心血管疾病的诱发因素。因此，mLOY不仅为众多慢病的发生发展提供了共同的遗传学基础，也为研究人类寿命与疾病风险中的性别差异提供了新的内核。本文首先简述了LOY驱动克隆性造血的人群队列研究进展，随后梳理出mLOY的危险因素、检测方法和小鼠模型的构建策略，并总结了mLOY诱发多种重大慢病的潜在分子机制，最后对mLOY领域的挑战和发展机遇提出了前瞻展望。相关综述成果为深入研究ChrY的生物学功能和慢病的性别差异提供参考。

关键词: 嵌合型Y染色体丢失, 克隆性造血, 阿尔茨海默病, 白血病, 心血管疾病

Abstract:

Mosaic loss of Y Chromosome (mLOY) refers to genetic mosaicism in males where some somatic cells have lost the Y chromosome (ChrY) while other cells remain their ChrY. mLOY is primarily found in the blood, not only because blood cells are easily accessible, but also because hematopoietic stem cells with LOY mutation gain competitive advantages, therefore producing a large number of LOY-positive blood cells via clonal hematopoiesis. Due to the specific structures, human ChrY is prone to be missegregated during mitosis, and driving by the germline variants, environmental insults and aging microenvironments, mLOY becomes the most commonly acquired age-related mutation in male genomes. Population-based cohort studies have shown that men with a certain degree of mLOY is associated with significantly reduced life expectancy and increased risks of cancer, Alzheimer’s disease, cardiovascular diseases and among others. Recent studies using mouse models have further demonstrated that mLOY is a driving factor of leukemia and cardiovascular diseases. These findings suggest that mLOY not only provides a common genetic explanation for the occurrence of many chronic diseases in men, but also provides a new kernel for studying sex differences in human lifespan and disease risk. Here, we briefly summarize the findings from the population-based cohort studies on clonal hematopoiesis driven by LOY. Subsequently we sort out the risk factors of mLOY, methods for detecting mLOY and developing mLOY mouse models, and the potential mechanisms of mLOY in promoting a myriad of chronic diseases. Finally, we provide our own forward-looking perspectives for the future challenges and opportunities in mLOY. The findings from this review provide references for studying the biological role of Y chromosome and sex difference of chronic diseases.

Key words: mosaic loss of Y chromosome, clonal hematopoiesis, Alzheimer’s disease, leukemia, cardiovascular diseases

朱丽娜, 汪旭, 郭锡汉. 造血系统嵌合型Y染色体丢失：从人群队列到致病机制[J]. 遗传, 2025, 47(4): 409-427.

Lina Zhu, Xu Wang, Xihan Guo. Hematopoietic mosaic loss of Y chromosome: from population cohorts to pathogenic mechanisms[J]. Hereditas(Beijing), 2025, 47(4): 409-427.

图/表 7

图1

图2

表1

图3

图4

表2

大规模人群队列血液中mLOY与各类慢病研究汇总"

人群来源	研究疾病	与疾病的相关性	检测方法	检测位点	主要科学发现	参考文献
德国	骨髓增生异常综合征	P=0.005	FISH	Yq12	mLOY外周血细胞在年龄相关易感性骨髓增生异常综合征中是克隆性的。	[55]
德国	年龄相关黄斑变性	P=1.60e-08	SNP微阵列	ChrY: 2694521-59034049	mLOY与年龄相关黄斑变性风险存在相关性。	[62]
荷兰	心血管疾病	P=0.02	SNP微阵列、RT-PCR	TSPY1	在严重动脉粥样硬化人群中，血液中的mLOY与继发性心血管疾病独立相关。	[63]
美国	膀胱癌、肺癌和前列腺癌	P=0.12	SNP微阵列、 WGS	ChrY: 6671498-22919969	mLOY作为男性3种常见癌症的强危险因素的证据有限，并且没有观察到其与癌症诊断后生存率的关联。	[13]
马其顿	前列腺癌、结直肠癌	P=1.17×10^-9	QF-PCR	AMELY、AMELX	外周血白细胞中mLOY与前列腺癌、结直肠癌发生风险显著相关。	[57]
瑞典	非血液癌	P=0.003	SNP微阵列	ChrY: 2694521-59034049	mLOY与全因死亡率和非血液学癌症死亡率的风险相关。	[44]
瑞典	阿尔茨海默病	P=0.0184	SNP微阵列	ChrY: 2694521-59034049	阿尔茨海默病患者mLOY流行率是非阿尔茨海默病群体的2.8倍。	[21]
瑞典、波兰	阿尔茨海默病、前列腺癌	P=0.0026	SNP微阵列、ddPCR、WGS	ChrY: 2694521-59034049； AMELY、AMELX	阿尔茨海默病患者和前列腺癌患者的自然杀伤细胞和CD4⁺T淋巴细胞中有更多的mLOY。	[64]
西班牙	由冠状病毒2引起的严重急性呼吸系统综合征	P=0.004	SNP微阵列	PAR1、PAR2	具有克隆嵌合事件(嵌合染色体改变和/或mLOY)的个体显示新冠肺炎致死风险增加了54%。	[65]
意大利	自身免疫甲状腺炎	P=0.037	FISH	DYZ3、DYZ1	患自身免疫甲状腺炎男性血液中mLOY更高且这种现象随着年龄的增长而增加。	[53]
意大利	原发性胆汁肝硬化	P=0.0038	FISH	DYZ3、DYZ1	患原发性胆汁肝硬化男性血液中mLOY更高且这种现象随着年龄的增长而增加。	[54]
英国	糖尿病、心血管疾病或中风	P=0.0065	SNP微阵列	ChrY: 2658271-28767492	mLOY与一些健康相关因素(即酒精、体重指数、吸烟、糖尿病和中风)以及种族有关。	[10]
	肺癌	P=0.002	SNP微阵列	ChrY: 2658271-28767492	外周血白细胞中mLOY与肺癌发生风险增加相关。	[66]
	糖尿病、高血压和血胆固醇过多症	P=6.71×10^-7P<5×10^-324	SNP微阵列	-	mLOY与循环血细胞总数之间存在显著的人群关联。	[9]
	心血管疾病	P=0.001	SNP微阵列	ChrY: 2649520-59034050	mLOY白细胞中与男性由心血管疾病引起的死亡相关。	[12]
中国	急性髓系白血病	P=0.048	核型分析	-	在接受高剂量阿糖胞苷治疗的男性患者中，mLOY与急性髓系白血病高复发风险相关。	[67]
	肺癌	P=2.03×10^-2	SNP微阵列	ChrY: 2694521-59034049	非吸烟男性血液中自发性LOY与健康个体肺癌风险降低以及肺癌患者更好的预后密切相关，而在吸烟群体中并未发现相关性。	[68]
	精神分裂症	-	ddPCR	AMELY、AMELX	在中国汉族人群中，精神分裂症组与对照组之间的外周血mLOY无显著性差异。	[69]
	肺癌	P=0.046	SNP微阵列	-	携带mLOY尤其是克隆性mLOY会显著增加肺癌的发病风险。	[16]

表2

图5

参考文献 88

[1]	Rhie A, Nurk S, Cechova M, Hoyt SJ, Taylor DJ, Altemose N, Hook PW, Koren S, Rautiainen M, Alexandrov IA, Allen J, Asri M, Bzikadze AV, Chen NC, Chin CS, Diekhans M, Flicek P, Formenti G, Fungtammasan A, Giron CG, Garrison E, Gershman A, Gerton JL, Grady PGS, Guarracino A, Haggerty L, Halabian R, Hansen NF, Harris R, Hartley GA, Harvey WT, Haukness M, Heinz J, Hourlier T, Hubley RM, Hunt SE, Hwang S, Jain M, Kesharwani RK, Lewis AP, Li H, Logsdon GA, Lucas JK, Makalowski W, Markovic C, Martin FJ, Cartney AMM, McCoy RC, McDaniel J, McNulty BM, Medvedev P, Mikheenko A, Munson KM, Murphy TD, Olsen HE, Olson ND, Paulin LF, Porubsky D, Potapova T, Ryabov F, Salzberg SL, Sauria MEG, Sedlazeck FJ, Shafin K, Shepelev VA, Shumate A, Storer JM, Surapaneni L, Oill AMT, Thibaud-Nissen F, Timp W, Tomaszkiewicz M, Vollger MR, Walenz BP, Watwood AC, Weissensteiner MH, Wenger AM, Wilson MA, Zarate S, Zhu YM, Zook JM, Eichler EE, O'Neill RJ, Schatz MC, Miga KH, Makova KD, Phillippy AM. The complete sequence of a human Y chromosome. Nature, 2023, 621(7978): 344-354. pmid: 37612512
[2]	Cortez D, Marin R, Toledo-Flores D, Froidevaux L, Liechti A, Waters PD, Grützner F, Kaessmann H. Origins and functional evolution of Y chromosomes across mammals. Nature, 2014, 508(7497): 488-493. pmid: 24759410
[3]	Bellott DW, Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Cho TJ, Koutseva N, Zaghlul S, Graves T, Rock S, Kremitzki C, Fulton RS, Dugan S, Ding Y, Morton D, Khan Z, Lewis L, Buhay C, Wang QY, Watt J, Holder M, Lee S, Nazareth L, Alföldi J, Rozen S, Muzny DM, Warren WC, Gibbs RA, Wilson RK, Page DC. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature, 2014, 508(7497): 494-499. pmid: 24759411
[4]	Yang XR, Wang MQ, Li SH. The evolution of human Y chromosome. Hereditas(Beijing), 2014, 36(9): 849-856.
	杨仙荣, 王美琴, 李少华. 人类Y染色体的演化. 遗传, 2014, 36(9): 849-856.
[5]	Guo XH, Dai XQ, Zhou T, Wang H, Ni J, Xue JL, Wang X. Mosaic loss of human Y chromosome: what, how and why. Hum Genet, 2020, 139(4): 421-446. pmid: 32020362
[6]	Dai XQ, Guo XH. Decoding and rejuvenating human ageing genomes: lessons from mosaic chromosomal alterations. Ageing Res Rev, 2021, 68: 101342. pmid: 33866012
[7]	Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science, 2019, 366(6465): eaan4673. pmid: 31672865
[8]	Baliakas P, Forsberg LA. Chromosome Y loss and drivers of clonal hematopoiesis in myelodysplastic syndrome. Haematologica, 2021, 106(2): 329-331. pmid: 33522783
[9]	Lin SH, Loftfield E, Sampson JN, Zhou WY, Yeager M, Freedman ND, Chanock SJ, Machiela MJ. Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men. Sci Rep, 2020, 10(1): 3655. pmid: 32108144
[10]	Loftfield E, Zhou WY, Graubard BI, Yeager M, Chanock SJ, Freedman ND, Machiela MJ. Predictors of mosaic chromosome Y loss and associations with mortality in the UK Biobank. Sci Rep, 2018, 8(1): 12316. pmid: 30120341
[11]	Zhang Q, Zhao L, Yang Y, Li SJ, Liu Y, Chen C. Mosaic loss of chromosome Y promotes leukemogenesis and clonal hematopoiesis. JCI Insight, 2022, 7(3): e153768. pmid: 35132955
[12]	Sano S, Horitani K, Ogawa H, Halvardson J, Chavkin NW, Wang Y, Sano M, Mattisson J, Hata A, Danielsson M, Miura-Yura E, Zaghlool A, Evans MA, Fall T, De Hoyos HN, Sundström J, Yura Y, Kour A, Arai Y, Thel MC, Arai Y, Mychaleckyj JC, Hirschi KK, Forsberg LA, Walsh K. Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality. Science, 2022, 377(6603): 292-297. pmid: 35857592
[13]	Zhou WY, Machiela MJ, Freedman ND, Rothman N, Malats N, Dagnall C, Caporaso N, Teras LT, Gaudet MM, Gapstur SM, Stevens VL, Jacobs KB, Sampson J, Albanes D, Weinstein S, Virtamo J, Berndt S, Hoover RN, Black A, Silverman D, Figueroa J, Garcia-Closas M, Real FX, Earl J, Marenne G, Rodriguez-Santiago B, Karagas M, Johnson A, Schwenn M, Wu XF, Gu J, Ye YQ, Hutchinson A, Tucker M, Perez-Jurado LA, Dean M, Yeager M, Chanock SJ. Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat Genet, 2016, 48(5): 563-568. pmid: 27064253
[14]	Wang WX, Huang T, Li LM. Construction and application of human genetic resources in the China Kadoorie Biobank. Hereditas(Beijing), 2021, 43(10): 972-979.
	王文秀, 黄涛, 李立明. 基于“中国慢性病前瞻性研究”的遗传资源建设与应用. 遗传, 2021, 43(10): 972-979.
[15]	Song MY, Zhao YX, Han YT, Lyu J, Yu CQ, Pei P, Du HD, Chen JS, Chen ZM, Sun DJY, Li LM. Epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration in adults from 10 regions of China. Chin J Epidemiol, 2023, 44(7): 1021-1026.
	宋明钰, 赵禹碹, 韩雨廷, 吕筠, 余灿清, 裴培, 杜怀东, 陈君石, 陈铮鸣, 孙点剑一, 李立明. 中国10个地区成年人外周血嵌合染色体变异的流行病学分布特征. 中华流行病学杂志, 2023, 44(7): 1021-1026.
[16]	Zhao YX, Song MY, Lyu J, Yu CQ, Pei P, Du HD, Chen JS, Chen ZM, Li LM, Sun DJY. Epidemiological distribution of mosaic loss of chromosome Y in adult men in 10 areas in China and its prospective association with lung cancer. Chin J Epidemiol, 2024, 45(1): 56-62
	赵禹碹, 宋明钰, 吕筠, 余灿清, 裴培, 杜怀东, 陈君石, 陈铮鸣, 李立明, 孙点剑一. 中国10个地区成年男性Y染色体嵌合缺失流行病学分布及其与肺癌的前瞻性关联研究. 中华流行病学杂志, 2024, 45(1): 56-62.
[17]	Danielsson M, Halvardson J, Davies H, Torabi Moghadam B, Mattisson J, Rychlicka-Buniowska E, Jaszczyński J, Heintz J, Lannfelt L, Giedraitis V, Ingelsson M, Dumanski JP, Forsberg LA. Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals. Eur J Hum Genet, 2020, 28(3): 349-357. pmid: 31654039
[18]	Zink F, Stacey SN, Norddahl GL, Frigge ML, Magnusson OT, Jonsdottir I, Thorgeirsson TE, Sigurdsson A, Gudjonsson SA, Gudmundsson J, Jonasson JG, Tryggvadottir L, Jonsson T, Helgason A, Gylfason A, Sulem P, Rafnar T, Thorsteinsdottir U, Gudbjartsson DF, Masson G, Kong A, Stefansson K. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood, 2017, 130(6): 742-752. pmid: 28483762
[19]	Jakubek YA, Ma XL, Stilp AM, Yu FL, Bacon J, Wong JW, Aguet F, Ardlie K, Arnett D, Barnes K, Bis JC, Blackwell T, Becker LC, Boerwinkle E, Bowler RP, Budoff MJ, Carson AP, Chen JW, Cho MH, Coresh J, Cox N, de Vries PS, DeMeo DL, Fardo DW, Fornage M, Guo XQ, Hall ME, Heard-Costa N, Hidalgo B, Irvin MR, Johnson AD, Kenny EE, Levy D, Li Y, Lima JA, Liu YM, Loos RJF, Machiela MJ, Mathias RA, Mitchell BD, Murabito J, Mychaleckyj JC, North K, Orchard P, Parker SC, Pershad Y, Peyser PA, Pratte KA, Psaty BM, Raffield LM, Redline S, Rich SS, Rotter JI, Shah SJ, Smith JA, Smith AP, Smith A, Taub M, Tiwari HK, Tracy R, Tuftin B, Bick AG, Sankaran VG, Reiner AP, Scheet P, Auer PL. Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood. medRxiv, 2024, doi: 10.1101/2024.04.16.24305851. pmid: 38699360
[20]	Terao C, Momozawa Y, Ishigaki K, Kawakami E, Akiyama M, Loh PR, Genovese G, Sugishita H, Ohta T, Hirata M, Perry JRB, Matsuda K, Murakami Y, Kubo M, Kamatani Y. GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation. Nat Commun, 2019, 10(1): 4719. pmid: 31624269
[21]	Dumanski JP, Lambert JC, Rasi C, Giedraitis V, Davies H, Grenier-Boley B, Lindgren CM, Campion D, Dufouil C, European Alzheimer’s Disease Initiative Investigators, Pasquier F, Amouyel P, Lannfelt L, Ingelsson M, Kilander L, Lind L, Forsberg LA. Mosaic loss of chromosome Y in blood is associated with Alzheimer’s disease. Am J Hum Genet, 2016, 98(6): 1208-1219. pmid: 27231129
[22]	Thompson DJ, Genovese G, Halvardson J, Ulirsch JC, Wright DJ, Terao C, Davidsson OB, Day FR, Sulem P, Jiang YX, Danielsson M, Davies H, Dennis J, Dunlop MG, Easton DF, Fisher VA, Zink F, Houlston RS, Ingelsson M, Kar S, Kerrison ND, Kinnersley B, Kristjansson RP, Law PJ, Li R, Loveday C, Mattisson J, McCarroll SA, Murakami Y, Murray A, Olszewski P, Rychlicka- Buniowska E, Scott RA, Thorsteinsdottir U, Tomlinson I, Moghadam BT, Turnbull C, Wareham NJ, Gudbjartsson DF, International Lung Cancer Consortium (INTEGRAL- ILCCO), Breast Cancer Association Consortium, Consortium of Investigators of Modifiers of BRCA1/2, Endometrial Cancer Association Consortium, Ovarian Cancer Association Consortium, Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) Consortium, Kidney Cancer GWAS Meta-Analysis Project, eQTLGen Consortium, Biobank-based Integrative Omics Study (BIOS) Consortium, 23andMe Research Team, Kamatani Y, Hoffmann ER, Jackson SP, Stefansson K, Auton A, Ong KK, Machiela MJ, Loh PR, Dumanski JP, Chanock SJ, Forsberg LA, Perry JRB. Genetic predisposition to mosaic Y chromosome loss in blood. Nature, 2019, 575(7784): 652-657. pmid: 31748747
[23]	Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Graves T, Fulton RS, Dugan S, Ding Y, Buhay CJ, Kremitzki C, Wang QY, Shen H, Holder M, Villasana D, Nazareth LV, Cree A, Courtney L, Veizer J, Kotkiewicz H, Cho TJ, Koutseva N, Rozen S, Muzny DM, Warren WC, Gibbs RA, Wilson RK, Page DC. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature, 2012, 483(7387): 82-86. pmid: 22367542
[24]	Hughes JF, Skaletsky H, Koutseva N, Pyntikova T, Page DC. Sex chromosome-to-autosome transposition events counter Y-chromosome gene loss in mammals. Genome Biol, 2015, 16(1): 104. pmid: 26017895
[25]	San Roman AK, Skaletsky H, Godfrey AK, Bokil NV, Teitz L, Singh I, Blanton LV, Bellott DW, Pyntikova T, Lange J, Koutseva N, Hughes JF, Brown L, Phou S, Buscetta A, Kruszka P, Banks N, Dutra A, Pak E, Lasutschinkow PC, Keen C, Davis SM, Lin AE, Tartaglia NR, Samango-Sprouse C, Muenke M, Page DC. The human Y and inactive X chromosomes similarly modulate autosomal gene expression. Cell Genom, 2024, 4(1): 100462. pmid: 38190107
[26]	Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, Chinwalla A, Delehaunty A, Delehaunty K, Du H, Fewell G, Fulton L, Fulton R, Graves T, Hou SF, Latrielle P, Leonard S, Mardis E, Maupin R, McPherson J, Miner T, Nash W, Nguyen C, Ozersky P, Pepin K, Rock S, Rohlfing T, Scott K, Schultz B, Strong C, Tin-Wollam A, Yang SP, Waterston RH, Wilson RK, Rozen S, Page DC. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 2003, 423(6942): 825-837. pmid: 12815422
[27]	Jobling MA, Tyler-Smith C. Human Y-chromosome variation in the genome-sequencing era. Nat Rev Genet, 2017, 18(8): 485-497. pmid: 28555659
[28]	Rogers MJ. Y chromosome copy number variation and its effects on fertility and other health factors: a review. Transl Androl Urol, 2021, 10(3): 1373-1382. pmid: 33850773
[29]	Hallast P, Ebert P, Loftus M, Yilmaz F, Audano PA, Logsdon GA, Bonder MJ, Zhou WC, Höps W, Kim K, Li C, Hoyt SJ, Dishuck PC, Porubsky D, Tsetsos F, Kwon JY, Zhu QH, Munson KM, Hasenfeld P, Harvey WT, Lewis AP, Kordosky J, Hoekzema K, Human Genome Structural Variation Consortium (HGSVC), O'Neill RJ, Korbel JO, Tyler-Smith C, Eichler EE, Shi XH, Beck CR, Marschall T, Konkel MK, Lee C. Assembly of 43 human Y chromosomes reveals extensive complexity and variation. Nature, 2023, 621(7978): 355-364. pmid: 37612510
[30]	Nath J, Tucker JD, Hando JC. Y chromosome aneuploidy, micronuclei, kinetochores and aging in men. Chromosoma, 1995, 103(10): 725-731. pmid: 7664620
[31]	Zhang C, Wang X, Guo XH. The origin and biomedical implications of immunogenic micronucleus. Chin Bull Life Sci, 2022, 34(4): 392-400.
	张城, 汪旭, 郭锡汉. 免疫原性微核的起源与生物医学意义. 生命科学, 2022, 34(4): 392-400.
[32]	Adams DJ, Barlas B, McIntyre RE, Salguero I, van der Weyden L, Barros A, Vicente JR, Karimpour N, Haider A, Ranzani M, Turner G, Thompson NA, Harle V, Olvera-León R, Robles-Espinoza CD, Speak AO, Geisler N, Weninger WJ, Geyer SH, Hewinson J, Karp NA, Sanger Mouse Genetics Project, Fu B, Yang F, Kozik Z, Choudhary J, Yu L, van Ruiten MS, Rowland BD, Lelliott CJ, Velasco-Herrera MDC, Verstraten R, Bruckner L, Henssen AG, Rooimans MA, de Lange J, Mohun TJ, Arends MJ, Kentistou KA, Coelho PA, Zhao Y, Zecchini H, Perry JRB, Jackson SP, Balmus G. Genetic determinants of micronucleus formation in vivo. Nature, 2024, 627(8002): 130-136. pmid: 38355793
[33]	Dumont M, Gamba R, Gestraud P, Klaasen S, Worrall JT, De Vries SG, Boudreau V, Salinas-Luypaert C, Maddox PS, Lens SM, Kops GJ, McClelland SE, Miga KH, Fachinetti D. Human chromosome-specific aneuploidy is influenced by DNA-dependent centromeric features. EMBO J, 2020, 39(2): e102924. pmid: 31750958
[34]	Lange J, Skaletsky H, Embry SL, Korver CM, Brown LG, Oates RD, Silber S, Repping S, Page DC. Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes. Cell, 2009, 138(5): 855-869. pmid: 19737515
[35]	Colaco S, Modi D. Genetics of the human Y chromosome and its association with male infertility. Reprod Biol Endocrinol, 2018, 16(1): 14. pmid: 29454353
[36]	Wright DJ, Day FR, Kerrison ND, Zink F, Cardona A, Sulem P, Thompson DJ, Sigurjonsdottir S, Gudbjartsson DF, Helgason A, Chapman JR, Jackson SP, Langenberg C, Wareham NJ, Scott RA, Thorsteindottir U, Ong KK, Stefansson K, Perry JRB. Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility. Nat Genet, 2017, 49(5): 674-679. pmid: 28346444
[37]	Petry S. Mechanisms of mitotic spindle assembly. Annu Rev Biochem, 2016, 85(1): 659-683. pmid: 27145846
[38]	Godek KM, Kabeche L, Compton DA. Regulation of kinetochore-microtubule attachments through homeostatic control during mitosis. Nat Rev Mol Cell Biol, 2015, 16(1): 57-64. pmid: 25466864
[39]	Hirota T, Gerlich D, Koch B, Ellenberg J, Peters JM. Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci, 2004, 117(Pt 26): 6435-6445. pmid: 15572404
[40]	Laine J, Künstle G, Obata T, Sha M, Noguchi M. The protooncogene TCL1 is an akt kinase coactivator. Mol Cell, 2000, 6(2): 395-407. pmid: 10983986
[41]	Chen XD, Jiang YF, Xu P, Jin L. Construction and utilization of human genetic resources in large population cohorts. Hereditas(Beijing), 2021, 43(10): 980-987.
	陈兴栋, 蒋艳峰, 徐萍, 金力. 大型人群队列遗传资源建设与利用. 遗传, 2021, 43(10): 980-987.
[42]	Luo W, Hou ZL, Guo YF. Research progress of genetic resources investigation of ethnic minorities. Chin Bull Life Sci, 2023, 35(12): 1586-1593.
	罗薇, 侯宗柳, 郭洋帆. 少数民族遗传资源调查研究进展. 生命科学, 2023, 35(12): 1586-1593.
[43]	Dumanski JP, Rasi C, Lönn M, Davies H, Ingelsson M, Giedraitis V, Lannfelt L, Magnusson PKE, Lindgren CM, Morris AP, Cesarini D, Johannesson M, Janson ET, Lind L, Pedersen NL, Ingelsson E, Forsberg LA. Smoking is associated with mosaic loss of chromosome Y. Science, 2015, 347(6217): 81-83. pmid: 25477213
[44]	Forsberg LA, Rasi C, Malmqvist N, Davies H, Pasupulati S, Pakalapati G, Sandgren J, de Ståhl TD, Zaghlool A, Giedraitis V, Lannfelt L, Score J, Cross NCP, Absher D, Janson ET, Lindgren CM, Morris AP, Ingelsson E, Lind L, Dumanski JP. Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. Nat Genet, 2014, 46(6): 624-628. pmid: 24777449
[45]	Wong JYY, Margolis HG, Machiela M, Zhou WY, Odden MC, Psaty BM, Robbins J, Jones RR, Rotter JI, Chanock SJ, Rothman N, Lan Q, Lee JS. Outdoor air pollution and mosaic loss of chromosome Y in older men from the cardiovascular health study. Environ Int, 2018, 116(1): 239-247. pmid: 29698900
[46]	Chang VC, Zhou WY, Berndt SI, Andreotti G, Yeager M, Parks CG, Sandler DP, Rothman N, Beane Freeman LE, Machiela MJ, Hofmann JN. Glyphosate use and mosaic loss of chromosome Y among male farmers in the agricultural health study. Environ Health Perspect, 2023, 131(12): 127006. pmid: 38055050
[47]	Liu YH, Bai YS, Wu XL, Li GYN, Wei W, Fu WS, Wang GG, Feng Y, Meng H, Li H, Li MY, Guan X, Zhang XM, He MA, Wu TC, Guo H. Polycyclic aromatic hydrocarbons exposure and their joint effects with age, smoking, and TCL1A variants on mosaic loss of chromosome Y among coke-oven workers. Environ Pollut, 2020, 258(1): 113655. pmid: 31818624
[48]	Bai YS, Guan X, Wei W, Feng Y, Meng H, Li GYN, Li H, Li MY, Wang CM, Fu M, Jie JL, Zhang XM, He MA, Guo H. Effects of polycyclic aromatic hydrocarbons and multiple metals co-exposure on the mosaic loss of chromosome Y in peripheral blood. J Hazard Mater, 2021, 414(1): 125519. pmid: 33676251
[49]	Guan X, Meng X, Zhong GR, Zhang ZR, Wang CM, Xiao Y, Fu M, Zhao H, Zhou YH, Hong SR, Xu XD, Bai YS, Kan HD, Chen RJ, Wu TC, Guo H. Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study. J Hazard Mater, 2024, 471: 134315. pmid: 38678703
[50]	Demanelis K, Delgado DA, Tong L, Jasmine F, Ahmed A, Islam T, Parvez F, Kibriya MG, Graziano JH, Ahsan H, Pierce BL. Somatic loss of the Y chromosome is associated with arsenic exposure among bangladeshi men. Int J Epidemiol, 2023, 52(4): 1035-1046. pmid: 36130227
[51]	Young K, Eudy E, Bell R, Loberg MA, Stearns T, Sharma D, Velten L, Haas S, Filippi MD, Trowbridge JJ. Decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging. Cell Stem Cell, 2021, 28(8): 1473-1482.e7. pmid: 33848471
[52]	Jacobs PA, Brunton M, Court Brown WM, Doll R, Goldstein H. Change of human chromosome count distribution with age: evidence for a sex differences. Nature, 1963, 197(4872): 1080-1081. pmid: 13964326
[53]	Persani L, Bonomi M, Lleo A, Pasini S, Civardi F, Bianchi I, Campi I, Finelli P, Miozzo M, Castronovo C, Sirchia S, Gershwin ME, Invernizzi P. Increased loss of the Y chromosome in peripheral blood cells in male patients with autoimmune thyroiditis. J Autoimmun, 2012, 38(2-3): J193-J196. pmid: 22196921
[54]	Lleo A, Oertelt-Prigione S, Bianchi I, Caliari L, Finelli P, Miozzo M, Lazzari R, Floreani A, Donato F, Colombo M, Gershwin ME, Podda M, Invernizzi P. Y chromosome loss in male patients with primary biliary cirrhosis. J Autoimmun, 2013, 41: 87-91. pmid: 23375847
[55]	Ganster C, Kämpfe D, Jung K, Braulke F, Shirneshan K, Machherndl-Spandl S, Suessner S, Bramlage CP, Legler TJ, Koziolek MJ, Haase D, Schanz J. New data shed light on Y-loss-related pathogenesis in myelodysplastic syndromes. Genes Chromosomes Cancer, 2015, 54(12): 717-724. pmid: 26394808
[56]	Wells D, Kaur K, Grifo J, Glassner M, Taylor JC, Fragouli E, Munne S. Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation. J Med Genet, 2014, 51(8): 553-562. pmid: 25031024
[57]	Noveski P, Madjunkova S, Stefanovska ES, Geshkovska NM, Kuzmanovska M, Dimovski A, Plaseska-Karanfilska D. Loss of Y chromosome in peripheral blood of colorectal and prostate cancer patients. PLoS One, 2016, 11(1): e0146264. pmid: 26745889
[58]	Orta AH, Bush SJ, Gutiérrez-Mariscal M, Castro-Obregón S, Jaimes-Hoy L, Grande R, Vázquez G, Gorostieta-Salas E, Martínez-Pacheco M, Díaz-Barba K, Cornejo-Páramo P, Sanchez-Flores A, Székely T, Urrutia AO, Cortez D. Rats exhibit age-related mosaic loss of chromosome Y. Commun Biol, 2021, 4(1): 1418. pmid: 34934158
[59]	Mattisson J, Halvardson J, Davies H, Bruhn-Olszewska B, Olszewski P, Danielsson M, Bjurling J, Lindberg A, Zaghlool A, Rychlicka-Buniowska E, Dumanski JP, Forsberg LA. Loss of chromosome Y in regulatory T cells. BMC Genomics, 2024, 25(1): 243. pmid: 38443832
[60]	Zuo EW, Huo XN, Yao X, Hu XD, Sun YD, Yin JH, He BB, Wang X, Shi LY, Ping J, Wei Y, Ying WQ, Wei W, Liu WJ, Tang C, Li YX, Hu JZ, Yang H. CRISPR/ Cas9-mediated targeted chromosome elimination. Genome Biol, 2017, 18(1): 224. pmid: 29178945
[61]	Adikusuma F, Williams N, Grutzner F, Hughes J, Thomas P. Targeted deletion of an entire chromosome using CRISPR/Cas9. Mol Ther, 2017, 25(8): 1736-1738. pmid: 28633863
[62]	Grassmann F, Kiel C, den Hollander AI, Weeks DE, Lotery A, Cipriani V, Weber BHF, International Age-related Macular Degeneration Genomics Consortium (IAMDGC). Y chromosome mosaicism is associated with age-related macular degeneration. Eur J Hum Genet, 2019, 27(1): 36-41. pmid: 30158665
[63]	Haitjema S, Kofink D, Van Setten J, Van der Laan SW, Schoneveld AH, Eales J, Tomaszewski M, De Jager SCA, Pasterkamp G, Asselbergs FW, den Ruijter HM. Loss of Y chromosome in blood is associated with major cardiovascular events during follow-up in men after carotid endarterectomy. Circ Cardiovasc Genet, 2017, 10(4): e001544. pmid: 28768751
[64]	Dumanski JP, Halvardson J, Davies H, Rychlicka- Buniowska E, Mattisson J, Moghadam BT, Nagy N, Węglarczyk K, Bukowska-Strakova K, Danielsson M, Olszewski P, Piotrowski A, Ambicka A, Przewoźnik M, Bełch Ł, Grodzicki T, Chłosta PL, Imreh S, Giedraitis V, Lannfelt L, Kilander L, Nordlund J, Ameur A, Gyllensten U, Johansson Å, Józkowicz A, Siedlar M, Klich-Rączka A, Jaszczyński J, Enroth S, Baran J, Ingelsson M, Ryś J, Forsberg LA. Loss of Y in leukocytes, dysregulation of autosomal immune genes and disease risks. bioRxiv, 2019, doi: 10.1101/673459.
[65]	Pérez-Jurado LA, Cáceres A, Balagué-Dobón L, Esko T, López de Heredia M, Quintela I, Cruz R, Lapunzina P, Carracedo Á, SCOURGE Cohort Group, González JR. Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2. Commun Biol, 2024, 7(1): 202. pmid: 38374351
[66]	Loftfield E, Zhou WY, Yeager M, Chanock SJ, Freedman ND, Machiela MJ. Mosaic Y loss is moderately associated with solid tumor risk. Cancer Res, 2019, 79(3): 461-466. pmid: 30510122
[67]	Zhou W, Chen GF, Gong D, Li Y, Huang S, Wang N, Xu QY, Xiong Q, Jing Y, Lv N, Wang LL, Li YH, Yu L. Loss of the Y chromosome predicts a high relapse risk in younger adult male patients with t(8;21) acute myeloid leukemia on high-dose cytarabine consolidation therapy: a retrospective multicenter study. Leuk Lymphoma, 2020, 61(4): 820-830. pmid: 31724463
[68]	Qin N, Li N, Wang C, Pu ZN, Ma ZJ, Jin GF, Zhu M, Dai M, Hu ZB, Ma HX, Shen HB. Association of mosaic loss of chromosome Y with lung cancer risk and prognosis in a Chinese population. J Thorac Oncol, 2019, 14(1): 37-44. pmid: 30267841
[69]	Jiang LR, Song MY, Song F, Zhou YX, Yao HW, Li GQ, Luo HB. Characterization of loss of chromosome Y in peripheral blood cells in male Han Chinese patients with schizophrenia. BMC Psychiatry, 2023, 23(1): 469. pmid: 37370034
[70]	Cai YL, Liu JL, Wang B, Sun M, Yang H. Microglia in the neuroinflammatory pathogenesis of Alzheimer’s disease and related therapeutic targets. Front Immunol, 2022, 13(1): 856376. pmid: 35558075
[71]	García-González P, de Rojas I, Moreno-Grau S, Montrreal L, Puerta R, Alarcón-Martín E, Quintela I, Orellana A, Andrade V, Adami PVM, Heilmann-Heimbach S, Gomez- Garre P, Periñán MT, Alvarez I, Diez-Fairen M, Llaves RN, Roig CO, Garcia-Ribas G, Menéndez-González M, Martínez C, Aguilar M, Buongiorno M, Franco-Macías E, Saez ME, Cano A, Bullido MJ, Real LM, Rodríguez- Rodríguez E, Royo JL, Álvarez V, Pastor P, Piñol-Ripoll G, Mir P, Lara MC, Padilla MM, Sánchez-Juan P, Carracedo A, Valero S, Hernandez I, Tàrraga L, Ramirez A, Boada M, Ruiz A. Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men. Int J Mol Sci, 2023, 24(2): 898. pmid: 36674414
[72]	Dumanski JP, Halvardson J, Davies H, Rychlicka- Buniowska E, Mattisson J, Moghadam BT, Nagy N, Węglarczyk K, Bukowska-Strakova K, Danielsson M, Olszewski P, Piotrowski A, Oerton E, Ambicka A, Przewoźnik M, Bełch Ł, Grodzicki T, Chłosta PL, Imreh S, Giedraitis V, Kilander L, Nordlund J, Ameur A, Gyllensten U, Johansson Å, Józkowicz A, Siedlar M, Klich-Rączka A, Jaszczyński J, Enroth S, Baran J, Ingelsson M, Perry JRB, Ryś J, Forsberg LA. Immune cells lacking Y chromosome show dysregulation of autosomal gene expression. Cell Mol Life Sci, 2021, 78(8): 4019-4033. pmid: 33837451
[73]	Mattisson J, Danielsson M, Hammond M, Davies H, Gallant CJ, Nordlund J, Raine A, Edén M, Kilander L, Ingelsson M, Dumanski JP, Halvardson J, Forsberg LA. Leukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99. Sci Rep, 2021, 11(1): 15160. pmid: 34312421
[74]	Wang DL, Zhang SY, Li L, Liu X, Mei KR, Wang XQ. Structural insights into the assembly and activation of IL-1β with its receptors. Nat Immunol, 2010, 11(10): 905-911. pmid: 20802483
[75]	Luo LL, McGarvey P, Madhavan S, Kumar R, Gusev Y, Upadhyay G. Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome. Oncotarget, 2016, 7(10): 11165-11193. pmid: 26862846
[76]	Jiang MY, Wang X, Guo XH. Advances in the mechanistic study of Alzheimer’s disease pathogenesis regulated by microglia TREM2. Chin Bull Life Sci, 2023, 35(11): 1484-1497.
	姜敏艳, 汪旭, 郭锡汉. 小胶质细胞TREM2调控阿尔茨海默病发生的机制研究进展. 生命科学, 2023, 35(11): 1484-1497.
[77]	Vermeulen MC, Pearse R, Young-Pearse T, Mostafavi S. Mosaic loss of chromosome Y in aged human microglia. Genome Res, 2022, 32(10): 1795-1807. pmid: 36041859
[78]	Dubal DB. Sex difference in Alzheimer’s disease: an updated, balanced and emerging perspective on differing vulnerabilities. Handb Clin Neurol, 2020, 175(1): 261-273. pmid: 33008530
[79]	Gozdecka M, Meduri E, Mazan M, Tzelepis K, Dudek M, Knights AJ, Pardo M, Yu L, Choudhary JS, Metzakopian E, Iyer V, Yun HY, Park N, Varela I, Bautista R, Collord G, Dovey O, Garyfallos DA, De Braekeleer E, Kondo S, Cooper J, Göttgens B, Bullinger L, Northcott PA, Adams D, Vassiliou GS, Huntly BJP. UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. Nat Genet, 2018, 50(6): 883-894. pmid: 29736013
[80]	Möller-Leimkühler AM. Gender differences in cardiovascular disease and comorbid depression. Dialogues Clin Neurosci, 2007, 9(1): 71-83. pmid: 17506227
[81]	Horitani K, Chavkin NW, Arai Y, Wang Y, Ogawa H, Yura Y, Evans MA, Cochran JD, Thel MC, Polizio AH, Sano M, Miura-Yura E, Arai Y, Doviak H, Arnold AP, Gelfand BD, Hirschi KK, Sano S, Walsh K. Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure. Nat Cardiovasc Res, 2024, 3(3): 343-355. pmid: 39183958
[82]	Abdel-Hafiz HA, Schafer JM, Chen XY, Xiao T, Gauntner TD, Li ZH, Theodorescu D. Y chromosome loss in cancer drives growth by evasion of adaptive immunity. Nature, 2023, 619(7970): 624-631. pmid: 37344596
[83]	Müller P, Camacho OV, Yazbeck AM, Wölwer C, Zhai WW, Schumacher J, Heider D, Buettner R, Quaas A, Hillmer AM. Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome. Comput Struct Biotechnol J, 2023, 21(1): 1573-1583. pmid: 36874157
[84]	Qi MF, Pang JL, Mitsiades I, Lane AA, Rheinbay E. Loss of chromosome Y in primary tumors. Cell, 2023, 186(14): 3125-3136.e11.
[85]	Wilson PC, Verma A, Yoshimura Y, Muto Y, Li HK, Malvin NP, Dixon EE, Humphreys BD. Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease. Genome Biol, 2024, 25(1): 36. pmid: 38287344
[86]	Guo XH, Li JF, Xue JL, Fenech M, Wang X. Loss of Y chromosome: an emerging next-generation biomarker for disease prediction and early detection? Mutat Res Rev Mutat Res, 2021, 788: 108389. pmid: 34893154
[87]	Weyrich M, Cremer S, Gerster M, Sarakpi T, Rasper T, Zewinger S, Patyna SR, Leistner DM, Heine GH, Wanner C, März W, Fliser D, Dimmeler S, Zeiher AM, Speer T. Loss of Y chromosome and cardiovascular events in chronic kidney disease. Circulation, 2024, 150(10): 746-757. pmid: 39005209
[88]	Zekavat SM, Lin SH, Bick AG, Liu AX, Paruchuri K, Wang C, Uddin MM, Ye YX, Yu ZL, Liu XX, Kamatani Y, Bhattacharya R, Pirruccello JP, Pampana A, Loh PR, Kohli P, McCarroll SA, Kiryluk K, Neale B, Ionita-Laza I, Engels EA, Brown DW, Smoller JW, Green R, Karlson EW, Lebo M, Ellinor PT, Weiss ST, Daly MJ, Biobank Japan Project, FinnGen Consortium, Terao C, Zhao HY, Ebert BL, Reilly MP, Ganna A, Machiela MJ, Genovese G, Natarajan P. Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection. Nat Med, 2021, 27(6): 1012-1024. pmid: 34099924

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

人群来源	队列人数	环境暴露	携带mLOY人数(检出率)	环境暴露与mLOY相关性	检测方法	检测位点	主要科学发现	参考文献
瑞典	6,014	香烟	900(14.96%)	P=0.00094	SNP 微阵列	ChrY: 2694521-59034049	吸烟与血液中的mLOY有关，且吸烟对mLOY有短暂和剂量依赖的诱变效应。	[44]
美国	933	PM₁₀	66(7.1%)	P=0.03	SNP 微阵列	ChrY: 7502455-21979204	室外空气污染物如PM₁₀可能会增加白细胞中mLOY。	[45]
美国	1,606	草甘膦	342(21.3%)	P=0.07	SNP 微阵列	PAR	老年男性农民长期大量使用草甘膦可能与mLOY呈正相关。	[46]
中国	954	多环芳烃	23(2.4%)	P<0.05	SNP 微阵列	ChrY: 2655180-59034049	多环芳烃暴露与mLOY之间存在线性剂量效应关系。	[47]
	888	重金属 (1-OHNa, Sb, Mo)	-	P<0.01	SNP 微阵列	ChrY: 2655180-59034049	1-OHNa、Sb和Mo是与mLOY相关的重要的化学物质，其增加DNA损伤可能对血液mLOY增加有联合作用。	[48]
	10,158	PM_2.5	-	P<0.05	SNP 微阵列	ChrY: 2655180-59034049	PM_2.5暴露对mLOY有加速效应，并验证了PM₁₀对mLOY的有害影响。	[49]
孟加拉国	1,364	砷	178(13.05%)	P=0.065	SNP 微阵列	ChrY: 2 694521-59034049； 2781480-56887902	砷暴露与mLOY的增加有关；mLOY还与砷引起的皮肤损伤的风险增加有关。	[50]

造血系统嵌合型Y染色体丢失：从人群队列到致病机制

Hematopoietic mosaic loss of Y chromosome: from population cohorts to pathogenic mechanisms

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 88

相关文章 15

编辑推荐

Metrics

[1]	杨子玫, 张格, 魏刚, 经莉莉, 于明. AFF4在人类HEL细胞中广泛地影响RNA聚合酶II的停滞释放[J]. 遗传, 2023, 45(8): 658-668.
[2]	熊婉迪, 徐开宇, 陆林, 李家立. 长链非编码RNA在阿尔茨海默病中的研究进展[J]. 遗传, 2022, 44(3): 189-197.
[3]	孙兆庆, 闫波. 转录因子GATA6在心血管疾病中的作用及其调控机制[J]. 遗传, 2019, 41(5): 375-383.
[4]	于雪新,陈艾莉,李玥莹,刘丹,王前飞. 白血病的精准基因组医学研究与转化应用[J]. 遗传, 2018, 40(11): 988-997.
[5]	王永煜,余薇,周斌. Hippo信号通路与心血管发育及疾病调控[J]. 遗传, 2017, 39(7): 576-587.
[6]	曹丽娟,刘昕訸,查晴,宋倩,杨克,刘艳. SIRT3与细胞代谢及心血管疾病的相关性[J]. 遗传, 2015, 37(2): 111-120.
[7]	胡婉莉,高艾. 长链非编码RNA在血液系统肿瘤中作用的研究进展[J]. 遗传, 2015, 37(11): 1095-1104.
[8]	丁慧岳丽杰杨春兰. 次黄嘌呤鸟嘌呤磷酸核糖转移酶研究进展[J]. 遗传, 2013, 35(8): 948-954.
[9]	周雁，黄秋花. 白血病细胞中不同启动子驱动外源基因表达能力差异分析[J]. 遗传, 2011, 33(8): 879-885.
[10]	张玉，郑增长，葛军，张鸿雁，黄延旺，宋红生. 果蝇早老素基因的研究进展[J]. 遗传, 2011, 33(11): 1164-1170.
[11]	张鹏，王沥，杨泽，金锋. 老年痴呆关联基因的研究进展[J]. 遗传, 2003, 25(4): 445-449.
[12]	翁亚光，王应雄，刘学庆，何俊琳，陈雪梅，冯亚红. 小鼠子宫内膜LIF基因表达与雌、孕激素的关系[J]. 遗传, 2003, 25(1): 37-39.
[13]	李永青，朱传炳，袁婺洲，王跃群，吴秀山. 双色FISH和DNA纤维FISH方法的建立与应用[J]. 遗传, 2003, 25(1): 1-4.
[14]	黎刚，王应雄，刘学庆，翁亚光，何俊琳，陈雪梅. 原因不明性习惯性流产患者子宫蜕膜白血病抑制因子基因表达研究[J]. 遗传, 2002, 24(3): 251-253.
[15]	王应雄，何俊琳，翁亚光，刘学庆，陈雪梅，杨戎，魏莎莉，刘孝云. 习惯性流产胚胎绒毛细胞LIF基因的表达[J]. 遗传, 2001, 23(2): 111-113.