What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.

Ahmed Alfares; Lamia Alsubaie; Taghrid Aloraini; Aljoharah Alaskar; Azza Th. Althagafi; Ahmed Alahmad; Mamoon Rashid; Abdulrahman Alswaid; Ali Alothaim; Wafaa Eyaid; Faroug Ababneh; Mohammed Albalwi; Raniah Alotaibi; Mashael Almutairi; Nouf Altharawi; Alhanouf Alsamer; Marwa Abdelhakim; Senay Kafkas; Katsuhiko Mineta; Nicole Cheung; Abdallah Abdallah; Stine Büchmann-Møller; Yoshinori Fukasawa; Xiang Zhao; Issaac Rajan; Robert Hoehndorf; Fuad Al Mutairi; Takashi Gojobori; Majid Alfadhel

doi:10.1186/s12920-020-00743-8

What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.

Ahmed Alfares, Lamia Alsubaie, Taghrid Aloraini, Aljoharah Alaskar, Azza Th. Althagafi, Ahmed Alahmad, Mamoon Rashid, Abdulrahman Alswaid, Ali Alothaim, Wafaa Eyaid, Faroug Ababneh, Mohammed Albalwi, Raniah Alotaibi, Mashael Almutairi, Nouf Altharawi, Alhanouf Alsamer, Marwa Abdelhakim, Senay Kafkas, Katsuhiko Mineta, Nicole CheungAbdallah Abdallah, Stine Büchmann-Møller, Yoshinori Fukasawa, Xiang Zhao, Issaac Rajan, Robert Hoehndorf, Fuad Al Mutairi, Takashi Gojobori, Majid Alfadhel

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: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.

Original language	English (US)
Journal	BMC Medical Genomics
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s12920-020-00743-8
State	Published - Jul 19 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This research used resources from the Core Labs of King Abdullah University of Science and Technology (KAUST).

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https://repository.kaust.edu.sa/bitstream/10754/664333/1/Articlefile1.pdf

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Alfares, A., Alsubaie, L., Aloraini, T., Alaskar, A., Althagafi, A. T., Alahmad, A., Rashid, M., Alswaid, A., Alothaim, A., Eyaid, W., Ababneh, F., Albalwi, M., Alotaibi, R., Almutairi, M., Altharawi, N., Alsamer, A., Abdelhakim, M., Kafkas, S., Mineta, K., ... Alfadhel, M. (2020). What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations. BMC Medical Genomics, 13(1). https://doi.org/10.1186/s12920-020-00743-8

@article{b38c2de385514ddab52d0141affc29ca,

title = "What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.",

abstract = "BACKGROUND: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.",

author = "Ahmed Alfares and Lamia Alsubaie and Taghrid Aloraini and Aljoharah Alaskar and Althagafi, {Azza Th.} and Ahmed Alahmad and Mamoon Rashid and Abdulrahman Alswaid and Ali Alothaim and Wafaa Eyaid and Faroug Ababneh and Mohammed Albalwi and Raniah Alotaibi and Mashael Almutairi and Nouf Altharawi and Alhanouf Alsamer and Marwa Abdelhakim and Senay Kafkas and Katsuhiko Mineta and Nicole Cheung and Abdallah Abdallah and Stine B{\"u}chmann-M{\o}ller and Yoshinori Fukasawa and Xiang Zhao and Issaac Rajan and Robert Hoehndorf and {Al Mutairi}, Fuad and Takashi Gojobori and Majid Alfadhel",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This research used resources from the Core Labs of King Abdullah University of Science and Technology (KAUST).",

year = "2020",

month = jul,

day = "19",

doi = "10.1186/s12920-020-00743-8",

language = "English (US)",

volume = "13",

journal = "BMC Medical Genomics",

issn = "1755-8794",

publisher = "BioMed Central",

number = "1",

}

Alfares, A, Alsubaie, L, Aloraini, T, Alaskar, A, Althagafi, AT, Alahmad, A, Rashid, M, Alswaid, A, Alothaim, A, Eyaid, W, Ababneh, F, Albalwi, M, Alotaibi, R, Almutairi, M, Altharawi, N, Alsamer, A, Abdelhakim, M, Kafkas, S, Mineta, K, Cheung, N, Abdallah, A, Büchmann-Møller, S, Fukasawa, Y, Zhao, X, Rajan, I, Hoehndorf, R, Al Mutairi, F, Gojobori, T & Alfadhel, M 2020, 'What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.', BMC Medical Genomics, vol. 13, no. 1. https://doi.org/10.1186/s12920-020-00743-8

TY - JOUR

T1 - What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.

AU - Alfares, Ahmed

AU - Alsubaie, Lamia

AU - Aloraini, Taghrid

AU - Alaskar, Aljoharah

AU - Althagafi, Azza Th.

AU - Alahmad, Ahmed

AU - Rashid, Mamoon

AU - Alswaid, Abdulrahman

AU - Alothaim, Ali

AU - Eyaid, Wafaa

AU - Ababneh, Faroug

AU - Albalwi, Mohammed

AU - Alotaibi, Raniah

AU - Almutairi, Mashael

AU - Altharawi, Nouf

AU - Alsamer, Alhanouf

AU - Abdelhakim, Marwa

AU - Kafkas, Senay

AU - Mineta, Katsuhiko

AU - Cheung, Nicole

AU - Abdallah, Abdallah

AU - Büchmann-Møller, Stine

AU - Fukasawa, Yoshinori

AU - Zhao, Xiang

AU - Rajan, Issaac

AU - Hoehndorf, Robert

AU - Al Mutairi, Fuad

AU - Gojobori, Takashi

AU - Alfadhel, Majid

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This research used resources from the Core Labs of King Abdullah University of Science and Technology (KAUST).

PY - 2020/7/19

Y1 - 2020/7/19

N2 - BACKGROUND: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.

AB - BACKGROUND: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.

UR - http://hdl.handle.net/10754/664333

UR - https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-020-00743-8

U2 - 10.1186/s12920-020-00743-8

DO - 10.1186/s12920-020-00743-8

M3 - Article

C2 - 32680510

SN - 1755-8794

VL - 13

JO - BMC Medical Genomics

JF - BMC Medical Genomics

IS - 1

ER -

What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.

Abstract

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