View in EDS PDF Full Text

Health and population effects of rare gene knockouts in adult humans with related parents.

Saved in:
Bibliographic Details
Title: Health and population effects of rare gene knockouts in adult humans with related parents.
Authors: Narasimhan, Vagheesh M., Hunt, Karen A., Mason, Dan, Baker, Christopher L., Karczewski, Konrad J., Barnes, Michael R., Barnett, Anthony H., Bates, Chris, Bellary, Srikanth, Bockett, Nicholas A., Giorda, Kristina, Griffiths, Christopher J., Hemingway, Harry, Jia, Zhilong, Ann Kelly, M., Khawaja, Hajrah A., Lek, Monkol, McCarthy, Shane, McEachan, Rosie, O'Donnell-Luria, Anne
Source: Science (pre-March 2025). 4/22/2016, Vol. 352 Issue 6284, p474-477. 4p.
Subjects: Gene knockout, Genotypes, Nucleotide sequencing, Descent groups, Ethnic identity of British people
Abstract: Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Links:
  – Type: pdflink
Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 114783419
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Health and population effects of rare gene knockouts in adult humans with related parents.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Narasimhan%2C+Vagheesh+M%2E%22">Narasimhan, Vagheesh M.</searchLink><br /><searchLink fieldCode="AR" term="%22Hunt%2C+Karen+A%2E%22">Hunt, Karen A.</searchLink><br /><searchLink fieldCode="AR" term="%22Mason%2C+Dan%22">Mason, Dan</searchLink><br /><searchLink fieldCode="AR" term="%22Baker%2C+Christopher+L%2E%22">Baker, Christopher L.</searchLink><br /><searchLink fieldCode="AR" term="%22Karczewski%2C+Konrad+J%2E%22">Karczewski, Konrad J.</searchLink><br /><searchLink fieldCode="AR" term="%22Barnes%2C+Michael+R%2E%22">Barnes, Michael R.</searchLink><br /><searchLink fieldCode="AR" term="%22Barnett%2C+Anthony+H%2E%22">Barnett, Anthony H.</searchLink><br /><searchLink fieldCode="AR" term="%22Bates%2C+Chris%22">Bates, Chris</searchLink><br /><searchLink fieldCode="AR" term="%22Bellary%2C+Srikanth%22">Bellary, Srikanth</searchLink><br /><searchLink fieldCode="AR" term="%22Bockett%2C+Nicholas+A%2E%22">Bockett, Nicholas A.</searchLink><br /><searchLink fieldCode="AR" term="%22Giorda%2C+Kristina%22">Giorda, Kristina</searchLink><br /><searchLink fieldCode="AR" term="%22Griffiths%2C+Christopher+J%2E%22">Griffiths, Christopher J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hemingway%2C+Harry%22">Hemingway, Harry</searchLink><br /><searchLink fieldCode="AR" term="%22Jia%2C+Zhilong%22">Jia, Zhilong</searchLink><br /><searchLink fieldCode="AR" term="%22Ann+Kelly%2C+M%2E%22">Ann Kelly, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Khawaja%2C+Hajrah+A%2E%22">Khawaja, Hajrah A.</searchLink><br /><searchLink fieldCode="AR" term="%22Lek%2C+Monkol%22">Lek, Monkol</searchLink><br /><searchLink fieldCode="AR" term="%22McCarthy%2C+Shane%22">McCarthy, Shane</searchLink><br /><searchLink fieldCode="AR" term="%22McEachan%2C+Rosie%22">McEachan, Rosie</searchLink><br /><searchLink fieldCode="AR" term="%22O'Donnell-Luria%2C+Anne%22">O'Donnell-Luria, Anne</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 4/22/2016, Vol. 352 Issue 6284, p474-477. 4p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Gene+knockout%22">Gene knockout</searchLink><br /><searchLink fieldCode="DE" term="%22Genotypes%22">Genotypes</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotide+sequencing%22">Nucleotide sequencing</searchLink><br /><searchLink fieldCode="DE" term="%22Descent+groups%22">Descent groups</searchLink><br /><searchLink fieldCode="DE" term="%22Ethnic+identity+of+British+people%22">Ethnic identity of British people</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=114783419
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1126/science.aac8624
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 4
        StartPage: 474
    Subjects:
      – SubjectFull: Gene knockout
        Type: general
      – SubjectFull: Genotypes
        Type: general
      – SubjectFull: Nucleotide sequencing
        Type: general
      – SubjectFull: Descent groups
        Type: general
      – SubjectFull: Ethnic identity of British people
        Type: general
    Titles:
      – TitleFull: Health and population effects of rare gene knockouts in adult humans with related parents.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Narasimhan, Vagheesh M.
      – PersonEntity:
          Name:
            NameFull: Hunt, Karen A.
      – PersonEntity:
          Name:
            NameFull: Mason, Dan
      – PersonEntity:
          Name:
            NameFull: Baker, Christopher L.
      – PersonEntity:
          Name:
            NameFull: Karczewski, Konrad J.
      – PersonEntity:
          Name:
            NameFull: Barnes, Michael R.
      – PersonEntity:
          Name:
            NameFull: Barnett, Anthony H.
      – PersonEntity:
          Name:
            NameFull: Bates, Chris
      – PersonEntity:
          Name:
            NameFull: Bellary, Srikanth
      – PersonEntity:
          Name:
            NameFull: Bockett, Nicholas A.
      – PersonEntity:
          Name:
            NameFull: Giorda, Kristina
      – PersonEntity:
          Name:
            NameFull: Griffiths, Christopher J.
      – PersonEntity:
          Name:
            NameFull: Hemingway, Harry
      – PersonEntity:
          Name:
            NameFull: Jia, Zhilong
      – PersonEntity:
          Name:
            NameFull: Ann Kelly, M.
      – PersonEntity:
          Name:
            NameFull: Khawaja, Hajrah A.
      – PersonEntity:
          Name:
            NameFull: Lek, Monkol
      – PersonEntity:
          Name:
            NameFull: McCarthy, Shane
      – PersonEntity:
          Name:
            NameFull: McEachan, Rosie
      – PersonEntity:
          Name:
            NameFull: O'Donnell-Luria, Anne
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 22
              M: 04
              Text: 4/22/2016
              Type: published
              Y: 2016
          Identifiers:
            – Type: issn-print
              Value: 00368075
          Numbering:
            – Type: volume
              Value: 352
            – Type: issue
              Value: 6284
          Titles:
            – TitleFull: Science (pre-March 2025)
              Type: main
ResultId 1