Autozygome and high throughput confirmation of disease genes candidacy.
Autozygome and high throughput confirmation of disease genes candidacy.
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DOI：
10.1038/s41436-018-0138-x
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Alkuraya FS
中科院分区：
文献类型：
--
作者：
Maddirevula S;Alzahrani F;Al-Owain M;Al Muhaizea MA;Kayyali HR;AlHashem A;Rahbeeni Z;Al-Otaibi M;Alzaidan HI;Balobaid A;El Khashab HY;Bubshait DK;Faden M;Yamani SA;Dabbagh O;Al-Mureikhi M;Jasser AA;Alsaif HS;Alluhaydan I;Seidahmed MZ;Alabbasi BH;Almogarri I;Kurdi W;Akleh H;Qari A;Al Tala SM;Alhomaidi S;Kentab AY;Salih MA;Chedrawi A;Alameer S;Tabarki B;Shamseldin HE;Patel N;Ibrahim N;Abdulwahab F;Samira M;Goljan E;Abouelhoda M;Meyer BF;Hashem M;Shaheen R;AlShahwan S;Alfadhel M;Ben-Omran T;Al-Qattan MM;Monies D;Alkuraya FS
建立孟德尔表型和基因之间的联系使得能够正确解释其中的变体。自体染色体组是一种丰富的纯合突变体来源，已被成功地用于高通量鉴定新的常染色体隐性遗传病基因。在这里，我们强调了autocomalome的效用，用于高通量确认先前发表的与疾病的初步联系。疑似孟德尔表型患者的自体染色体组和外显子组分析。根据美国医学遗传学和基因组学学会指南对所有变体进行分类。我们突出30个已发表的候选基因（ACTL6B、ADAM 22、AGTPBP1、APC、C12orf4、C3orf17（NEPRO）、CENPF、CNPY3、COL27A1、DMBX1、FUT8、GOLGA 2、KIAA0556、LENG8、MCIDAS、MTMR 9、MYH11、QRSL1、RUBCN、SLC25A42、SLC9A1、TBXT、TFG、THUMPD1、TRAF3IP2、UFC 1、UFM 1、WDR 81、XRCC 2、ZAK），其中我们在具有相容表型的患者中鉴定了纯合的可能有害的变体。我们还在18个已发表的候选基因（ABCA 2、ARL6IP 1、ATP 8A2、CDK 9、CNKSR 1、DGAT 1、DMXL 2、GEMIN 4、HCN 2、HCRT、MYO 9A、PARS2、PLOD 3、PREPL、SCLT 1、STX 3、TXNRD 2、WIPI 2）中鉴定了纯合的可能有害的变体，尽管相关的表型与原始报告有很大不同，它们代表表型扩增或潜在的不同等位基因疾病。我们的研究结果将有助于在相关数据库中及时重新标记这些候选疾病基因，以提高临床基因组测序的产量。
Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases. Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines. We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently different from the original reports that they represent phenotypic expansion or potentially distinct allelic disorders. Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing.
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影响因子：
5.3
作者：
Monies D;Abouelhoda M;AlSayed M;Alhassnan Z;Alotaibi M;Kayyali H;Al-Owain M;Shah A;Rahbeeni Z;Al-Muhaizea MA;Alzaidan HI;Cupler E;Bohlega S;Faqeih E;Faden M;Alyounes B;Jaroudi D;Goljan E;Elbardisy H;Akilan A;Albar R;Aldhalaan H;Gulab S;Chedrawi A;Al Saud BK;Kurdi W;Makhseed N;Alqasim T;El Khashab HY;Al-Mousa H;Alhashem A;Kanaan I;Algoufi T;Alsaleem K;Basha TA;Al-Murshedi F;Khan S;Al-Kindy A;Alnemer M;Al-Hajjar S;Alyamani S;Aldhekri H;Al-Mehaidib A;Arnaout R;Dabbagh O;Shagrani M;Broering D;Tulbah M;Alqassmi A;Almugbel M;AlQuaiz M;Alsaman A;Al-Thihli K;Sulaiman RA;Al-Dekhail W;Alsaegh A;Bashiri FA;Qari A;Alhomadi S;Alkuraya H;Alsebayel M;Hamad MH;Szonyi L;Abaalkhail F;Al-Mayouf SM;Almojalli H;Alqadi KS;Elsiesy H;Shuaib TM;Seidahmed MZ;Abosoudah I;Akleh H;AlGhonaium A;Alkharfy TM;Al Mutairi F;Eyaid W;Alshanbary A;Sheikh FR;Alsohaibani FI;Alsonbul A;Al Tala S;Balkhy S;Bassiouni R;Alenizi AS;Hussein MH;Hassan S;Khalil M;Tabarki B;Alshahwan S;Oshi A;Sabr Y;Alsaadoun S;Salih MA;Mohamed S;Sultana H;Tamim A;El-Haj M;Alshahrani S;Bubshait DK;Alfadhel M;Faquih T;El-Kalioby M;Subhani S;Shah Z;Moghrabi N;Meyer BF;Alkuraya FS
通讯作者：
Alkuraya FS
影响因子：
12.3
作者：
Shaheen R;Szymanska K;Basu B;Patel N;Ewida N;Faqeih E;Al Hashem A;Derar N;Alsharif H;Aldahmesh MA;Alazami AM;Hashem M;Ibrahim N;Abdulwahab FM;Sonbul R;Alkuraya H;Alnemer M;Al Tala S;Al-Husain M;Morsy H;Seidahmed MZ;Meriki N;Al-Owain M;AlShahwan S;Tabarki B;Salih MA;Ciliopathy WorkingGroup;Faquih T;El-Kalioby M;Ueffing M;Boldt K;Logan CV;Parry DA;Al Tassan N;Monies D;Megarbane A;Abouelhoda M;Halees A;Johnson CA;Alkuraya FS
通讯作者：
Alkuraya FS
影响因子：
11.2
作者：
Shaheen, Ranad;Sebai, Mohammed Adeeb;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.
影响因子：
8.8
作者：
Monies, Dorota;Maddirevula, Sateesh;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.
影响因子：
4
作者：
Patel, Nisha;Faqeih, Eissa;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.