The University of Southampton
University of Southampton Institutional Repository

Homozygosity analysis in amyotrophic lateral sclerosis

Homozygosity analysis in amyotrophic lateral sclerosis
Homozygosity analysis in amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) may appear to be familial or sporadic, with recognised dominant and recessive inheritance in a proportion of cases. Sporadic ALS may be caused by rare homozygous recessive mutations. We studied patients and controls from the UK and a multinational pooled analysis of GWAS data on homozygosity in ALS to determine any potential recessive variant leading to the disease. Six-hundred and twenty ALS and 5169 controls were studied in the UK cohort. A total of 7646 homozygosity segments with length >2?Mb were identified, and 3568 rare segments remained after filtering ‘common’ segments. The mean total of the autosomal genome with homozygosity segments was longer in ALS than in controls (unfiltered segments, P=0.05). Two-thousand and seventeen ALS and 6918 controls were studied in the pooled analysis. There were more regions of homozygosity segments per case (P=1 × 10?5), a greater proportion of cases harboured homozygosity (P=2 × 10?5), a longer average length of segment (P=1 × 10?5), a longer total genome coverage (P=1 × 10?5), and a higher rate of these segments overlapped with RefSeq gene regions (P=1 × 10?5), in ALS patients than controls. Positive associations were found in three regions. The most significant was in the chromosome 21 SOD1 region, and also chromosome 1 2.9–4.8?Mb, and chromosome 5 in the 65?Mb region. There are more than twenty potential genes in these regions. These findings point to further possible rare recessive genetic causes of ALS, which are not identified as common variants in GWAS.
1018-4813
1429-1435
Mok, Kin
7182f816-7548-4a0c-80c7-bdb61c229a75
Laaksovirta, Hannu
9ef5371b-1a98-4ca4-8111-c64cf8e7ca12
Tienari, Pentti J.
fbbc5cb2-c75a-4fd2-adcc-28158ffc3ee1
Peuralinna, Terhi
bd5d9001-e521-4555-8fcb-e60f5ab905b7
Myllykangas, Liisa
8a72e3a4-d80b-47ad-90fa-fcc1f30d289c
Chiò, Adriano
9439830c-120e-46ba-ba44-838f4ab73d5a
Traynor, Bryan J.
45f36290-d228-40bb-8023-20af04f5fa1d
Nalls, Michael A.
63358c7d-9f85-4f10-923a-f3bf9bc03c68
Gurunlian, Nicole
88872f97-5124-41d5-8f2e-6c7d4f810634
Shatunov, Aleksey
e4422e0f-4878-404a-8e9e-fc45b4d5d9bd
Restagno, Gabriella
a367df06-5062-490c-8af4-1f80dce208dc
Mora, Gabriele
1fbe63af-6231-4cf8-97b6-88cf1abc8649
Leigh, P. Nigel
7f764ac0-9010-4831-9236-a40354cf61f9
Shaw, Chris E.
4c73e71a-70d1-4d3f-a08b-78d3e4a2d671
Morrison, Karen E.
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Shaw, Pamela J.
3d0a5c6f-9610-45be-a0bc-5b6888003028
Al-Chalabi, Ammar
db16bbda-7684-49b4-9b2d-9799c7dba33c
Hardy, John
7d6a3558-4b3a-4c69-953f-3f8a7d162dca
Orrell, Richard W.
ef3e7a42-0965-4f2f-9ab0-1a645b00b61f
Mok, Kin
7182f816-7548-4a0c-80c7-bdb61c229a75
Laaksovirta, Hannu
9ef5371b-1a98-4ca4-8111-c64cf8e7ca12
Tienari, Pentti J.
fbbc5cb2-c75a-4fd2-adcc-28158ffc3ee1
Peuralinna, Terhi
bd5d9001-e521-4555-8fcb-e60f5ab905b7
Myllykangas, Liisa
8a72e3a4-d80b-47ad-90fa-fcc1f30d289c
Chiò, Adriano
9439830c-120e-46ba-ba44-838f4ab73d5a
Traynor, Bryan J.
45f36290-d228-40bb-8023-20af04f5fa1d
Nalls, Michael A.
63358c7d-9f85-4f10-923a-f3bf9bc03c68
Gurunlian, Nicole
88872f97-5124-41d5-8f2e-6c7d4f810634
Shatunov, Aleksey
e4422e0f-4878-404a-8e9e-fc45b4d5d9bd
Restagno, Gabriella
a367df06-5062-490c-8af4-1f80dce208dc
Mora, Gabriele
1fbe63af-6231-4cf8-97b6-88cf1abc8649
Leigh, P. Nigel
7f764ac0-9010-4831-9236-a40354cf61f9
Shaw, Chris E.
4c73e71a-70d1-4d3f-a08b-78d3e4a2d671
Morrison, Karen E.
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Shaw, Pamela J.
3d0a5c6f-9610-45be-a0bc-5b6888003028
Al-Chalabi, Ammar
db16bbda-7684-49b4-9b2d-9799c7dba33c
Hardy, John
7d6a3558-4b3a-4c69-953f-3f8a7d162dca
Orrell, Richard W.
ef3e7a42-0965-4f2f-9ab0-1a645b00b61f

Mok, Kin, Laaksovirta, Hannu, Tienari, Pentti J., Peuralinna, Terhi, Myllykangas, Liisa, Chiò, Adriano, Traynor, Bryan J., Nalls, Michael A., Gurunlian, Nicole, Shatunov, Aleksey, Restagno, Gabriella, Mora, Gabriele, Leigh, P. Nigel, Shaw, Chris E., Morrison, Karen E., Shaw, Pamela J., Al-Chalabi, Ammar, Hardy, John and Orrell, Richard W. (2013) Homozygosity analysis in amyotrophic lateral sclerosis. European Journal of Human Genetics, 21 (12), 1429-1435. (doi:10.1038/ejhg.2013.59). (PMID:23612577)

Record type: Article

Abstract

Amyotrophic lateral sclerosis (ALS) may appear to be familial or sporadic, with recognised dominant and recessive inheritance in a proportion of cases. Sporadic ALS may be caused by rare homozygous recessive mutations. We studied patients and controls from the UK and a multinational pooled analysis of GWAS data on homozygosity in ALS to determine any potential recessive variant leading to the disease. Six-hundred and twenty ALS and 5169 controls were studied in the UK cohort. A total of 7646 homozygosity segments with length >2?Mb were identified, and 3568 rare segments remained after filtering ‘common’ segments. The mean total of the autosomal genome with homozygosity segments was longer in ALS than in controls (unfiltered segments, P=0.05). Two-thousand and seventeen ALS and 6918 controls were studied in the pooled analysis. There were more regions of homozygosity segments per case (P=1 × 10?5), a greater proportion of cases harboured homozygosity (P=2 × 10?5), a longer average length of segment (P=1 × 10?5), a longer total genome coverage (P=1 × 10?5), and a higher rate of these segments overlapped with RefSeq gene regions (P=1 × 10?5), in ALS patients than controls. Positive associations were found in three regions. The most significant was in the chromosome 21 SOD1 region, and also chromosome 1 2.9–4.8?Mb, and chromosome 5 in the 65?Mb region. There are more than twenty potential genes in these regions. These findings point to further possible rare recessive genetic causes of ALS, which are not identified as common variants in GWAS.

Full text not available from this repository.

More information

Accepted/In Press date: 28 February 2013
e-pub ahead of print date: 23 April 2013
Organisations: Medical Education

Identifiers

Local EPrints ID: 398459
URI: http://eprints.soton.ac.uk/id/eprint/398459
ISSN: 1018-4813
PURE UUID: e431b0b9-9e8d-4fb7-b4ac-30261c10c0fc
ORCID for Karen E. Morrison: ORCID iD orcid.org/0000-0003-0216-5717

Catalogue record

Date deposited: 25 Jul 2016 13:20
Last modified: 20 Jul 2019 00:33

Export record

Altmetrics

Contributors

Author: Kin Mok
Author: Hannu Laaksovirta
Author: Pentti J. Tienari
Author: Terhi Peuralinna
Author: Liisa Myllykangas
Author: Adriano Chiò
Author: Bryan J. Traynor
Author: Michael A. Nalls
Author: Nicole Gurunlian
Author: Aleksey Shatunov
Author: Gabriella Restagno
Author: Gabriele Mora
Author: P. Nigel Leigh
Author: Chris E. Shaw
Author: Pamela J. Shaw
Author: Ammar Al-Chalabi
Author: John Hardy
Author: Richard W. Orrell

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×