What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.
Althagafi, Azza Th.
Al Mutairi, Fuad
KAUST DepartmentBio-Ontology Research Group (BORG)
Biological and Environmental Sciences and Engineering (BESE) Division
Bioscience Core Lab
Computational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
NGS, qPCR and Single Cell Genomics
Sanger and Third Generation Sequencing
Online Publication Date2020-07-17
Print Publication Date2020-12
Permanent link to this recordhttp://hdl.handle.net/10754/664333
MetadataShow full item record
AbstractBACKGROUND:Testing strategies is crucial for genetics clinics and testing laboratories. In this study, we tried to compare the hit rate between solo and trio and trio plus testing and between trio and sibship testing. Finally, we studied the impact of extended family analysis, mainly in complex and unsolved cases. METHODS:Three cohorts were used for this analysis: one cohort to assess the hit rate between solo, trio and trio plus testing, another cohort to examine the impact of the testing strategy of sibship genome vs trio-based analysis, and a third cohort to test the impact of an extended family analysis of up to eight family members to lower the number of candidate variants. RESULTS:The hit rates in solo, trio and trio plus testing were 39, 40, and 41%, respectively. The total number of candidate variants in the sibship testing strategy was 117 variants compared to 59 variants in the trio-based analysis. We noticed that the average number of coding candidate variants in trio-based analysis was 1192 variants and 26,454 noncoding variants, and this number was lowered by 50-75% after adding additional family members, with up to two coding and 66 noncoding homozygous variants only, in families with eight family members. CONCLUSION:There was no difference in the hit rate between solo and extended family members. Trio-based analysis was a better approach than sibship testing, even in a consanguineous population. Finally, each additional family member helped to narrow down the number of variants by 50-75%. Our findings could help clinicians, researchers and testing laboratories select the most cost-effective and appropriate sequencing approach for their patients. Furthermore, using extended family analysis is a very useful tool for complex cases with novel genes.
CitationAlfares, A., Alsubaie, L., Aloraini, T., Alaskar, A., Althagafi, A., Alahmad, A., … Alfadhel, M. (2020). What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations. BMC Medical Genomics, 13(1). doi:10.1186/s12920-020-00743-8
SponsorsThis research used resources from the Core Labs of King Abdullah University of Science and Technology (KAUST).
JournalBMC medical genomics
RelationsIs Supplemented By:
Alfares, A., Alsubaie, L., Aloraini, T., Aljoharah Alaskar, Azza Althagafi, Alahmad, A., Mamoon Rashid, Abdulrahman Alswaid, Alothaim, A., Eyaid, W., Faroug Ababneh, Albalwi, M., Raniah Alotaibi, Mashael Almutairi, Nouf Altharawi, Alhanouf Alsamer, Abdelhakim, M., Senay Kafkas, Mineta, K., … Alfadhel, M. (2020). What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations. figshare. https://doi.org/10.6084/M9.FIGSHARE.C.5066525. DOI: 10.6084/m9.figshare.c.5066525 Handle: 10754/664972
CollectionsArticles; Bio-Ontology Research Group (BORG); Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Computer Science Program; Computational Bioscience Research Center (CBRC); Bioscience Core Lab; Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Except where otherwise noted, this item's license is described as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- When to think outside the autozygome: Best practices for exome sequencing in "consanguineous" families.
- Authors: Eaton A, Hartley T, Kernohan K, Ito Y, Lamont R, Parboosingh J, Barrowman N, Care4Rare consortium., Innes AM, Boycott K
- Issue date: 2020 Jun
- Second-tier trio exome sequencing after negative solo clinical exome sequencing: an efficient strategy to increase diagnostic yield and decipher molecular bases in undiagnosed developmental disorders.
- Authors: Tran Mau-Them F, Moutton S, Racine C, Vitobello A, Bruel AL, Nambot S, Kushner SA, de Vrij FMS, Lehalle D, Jean-Marçais N, Lecoquierre F, Delanne J, Thevenon J, Poe C, Jouan T, Chevarin M, Geneviève D, Willems M, Coubes C, Houcinat N, Masurel-Paulet A, Mosca-Boidron AL, Tisserant E, Callier P, Sorlin A, Duffourd Y, Faivre L, Philippe C, Thauvin-Robinet C
- Issue date: 2020 Nov
- The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
- Authors: 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
- Issue date: 2017 Aug
- Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.
- Authors: Reuter MS, Tawamie H, Buchert R, Hosny Gebril O, Froukh T, Thiel C, Uebe S, Ekici AB, Krumbiegel M, Zweier C, Hoyer J, Eberlein K, Bauer J, Scheller U, Strom TM, Hoffjan S, Abdelraouf ER, Meguid NA, Abboud A, Al Khateeb MA, Fakher M, Hamdan S, Ismael A, Muhammad S, Abdallah E, Sticht H, Wieczorek D, Reis A, Abou Jamra R
- Issue date: 2017 Mar 1
- Whole exome sequencing highlights variants in association with Keratoconus in Jordanian families.
- Authors: Froukh T, Hawwari A, Al Zubi K
- Issue date: 2020 Sep 4