Family-Specific Variants and the Limits of Human Genetics.
Family-Specific Variants and the Limits of Human Genetics.
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DOI：
10.1016/j.molmed.2016.09.007
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发表时间：
2016-11
影响因子：
13.6
通讯作者：
Walsh T
中科院分区：
文献类型：
--
作者：
Shirts BH;Pritchard CC;Walsh T
与生命相适应的每一个核苷酸变化都存在于今天的人类群体中。了解这些罕见的人类变异对遗传学和医学来说是一个非同寻常的挑战。对遗传性癌症风险的多个基因进行测序的新临床实践表明，临床下一代测序在成人中的应用，识别出比单基因测试更多的医学上可操作的变异。然而，它也揭示了所评估的DNA长度与所报道的罕见的“不确定意义的变体”数量之间的线性关系。我们建议，仔细地进行表型-基因推断，区分诊断和筛查意图，并扩大使用家庭规模的遗传学研究作为家庭特定变异的信息来源，将减少向患者报告的不确定意义的变异。
Every single nucleotide change compatible with life is present in the human population today. Understanding these rare human variants defines an extraordinary challenge for genetics and medicine. The new clinical practice of sequencing many genes for hereditary cancer risk has illustrated the utility of clinical next-generation sequencing in adults, identifying more medically actionable variants than single gene testing. However, it has also revealed a linear relationship between length of DNA evaluated and number of rare “variants of uncertain significance” reported. We propose that careful approaches to phenotype-genotype inference, distinguishing between diagnostic and screening intent, and expanded use of family-scale genetics studies as a source of information on family-specific variants will reduce variants of uncertain significance reported to patients.
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影响因子：
28.2
作者：
Kar SP;Beesley J;Amin Al Olama A;Michailidou K;Tyrer J;Kote-Jarai Z;Lawrenson K;Lindstrom S;Ramus SJ;Thompson DJ;ABCTB Investigators;Kibel AS;Dansonka-Mieszkowska A;Michael A;Dieffenbach AK;Gentry-Maharaj A;Whittemore AS;Wolk A;Monteiro A;Peixoto A;Kierzek A;Cox A;Rudolph A;Gonzalez-Neira A;Wu AH;Lindblom A;Swerdlow A;AOCS Study Group & Australian Cancer Study (Ovarian Cancer);APCB BioResource;Ziogas A;Ekici AB;Burwinkel B;Karlan BY;Nordestgaard BG;Blomqvist C;Phelan C;McLean C;Pearce CL;Vachon C;Cybulski C;Slavov C;Stegmaier C;Maier C;Ambrosone CB;Høgdall CK;Teerlink CC;Kang D;Tessier DC;Schaid DJ;Stram DO;Cramer DW;Neal DE;Eccles D;Flesch-Janys D;Edwards DR;Wokozorczyk D;Levine DA;Yannoukakos D;Sawyer EJ;Bandera EV;Poole EM;Goode EL;Khusnutdinova E;Høgdall E;Song F;Bruinsma F;Heitz F;Modugno F;Hamdy FC;Wiklund F;Giles GG;Olsson H;Wildiers H;Ulmer HU;Pandha H;Risch HA;Darabi H;Salvesen HB;Nevanlinna H;Gronberg H;Brenner H;Brauch H;Anton-Culver H;Song H;Lim HY;McNeish I;Campbell I;Vergote I;Gronwald J;Lubiński J;Stanford JL;Benítez J;Doherty JA;Permuth JB;Chang-Claude J;Donovan JL;Dennis J;Schildkraut JM;Schleutker J;Hopper JL;Kupryjanczyk J;Park JY;Figueroa J;Clements JA;Knight JA;Peto J;Cunningham JM;Pow-Sang J;Batra J;Czene K;Lu KH;Herkommer K;Khaw KT;kConFab Investigators;Matsuo K;Muir K;Offitt K;Chen K;Moysich KB;Aittomäki K;Odunsi K;Kiemeney LA;Massuger LF;Fitzgerald LM;Cook LS;Cannon-Albright L;Hooning MJ;Pike MC;Bolla MK;Luedeke M;Teixeira MR;Goodman MT;Schmidt MK;Riggan M;Aly M;Rossing MA;Beckmann MW;Moisse M;Sanderson M;Southey MC;Jones M;Lush M;Hildebrandt MA;Hou MF;Schoemaker MJ;Garcia-Closas M;Bogdanova N;Rahman N;NBCS Investigators;Le ND;Orr N;Wentzensen N;Pashayan N;Peterlongo P;Guénel P;Brennan P;Paulo P;Webb PM;Broberg P;Fasching PA;Devilee P;Wang Q;Cai Q;Li Q;Kaneva R;Butzow R;Kopperud RK;Schmutzler RK;Stephenson RA;MacInnis RJ;Hoover RN;Winqvist R;Ness R;Milne RL;Travis RC;Benlloch S;Olson SH;McDonnell SK;Tworoger SS;Maia S;Berndt S;Lee SC;Teo SH;Thibodeau SN;Bojesen SE;Gapstur SM;Kjær SK;Pejovic T;Tammela TL;GENICA Network;PRACTICAL consortium;Dörk T;Brüning T;Wahlfors T;Key TJ;Edwards TL;Menon U;Hamann U;Mitev V;Kosma VM;Setiawan VW;Kristensen V;Arndt V;Vogel W;Zheng W;Sieh W;Blot WJ;Kluzniak W;Shu XO;Gao YT;Schumacher F;Freedman ML;Berchuck A;Dunning AM;Simard J;Haiman CA;Spurdle A;Sellers TA;Hunter DJ;Henderson BE;Kraft P;Chanock SJ;Couch FJ;Hall P;Gayther SA;Easton DF;Chenevix-Trench G;Eeles R;Pharoah PD;Lambrechts D
通讯作者：
Lambrechts D
影响因子：
3.7
作者：
Chong, Hansook Kim;Wang, Tao;Elliott, Aaron M.
通讯作者：
Elliott, Aaron M.
影响因子：
9.8
作者：
Li, Jun;Woods, Susan L.;Chenevix-Trench, Georgia
通讯作者：
Chenevix-Trench, Georgia
影响因子：
16.8
作者：
Jeyasekharan, Anand D.;Liu, Yang;Hattori, Hiroyoshi;Pisupati, Venkat;Jonsdottir, Asta Bjork;Rajendra, Eeson;Lee, Miyoung;Sundaramoorthy, Elayanambi;Schlachter, Simon;Kaminski, Clemens F.;Rosenfeld, Yaara;Sato, Ko;Savill, Jane;Ayoub, Nabieh;Venkitaraman, Ashok R.
通讯作者：
Venkitaraman, Ashok R.
DOI：
10.1073/pnas.1511328112
发表时间：
2015-07-28
影响因子：
11.1
作者：
Kretz, Colin A.;Dai, Manhong;Ginsburg, David
通讯作者：
Ginsburg, David