A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries.
Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of...
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ftdoajarticles:oai:doaj.org/article:6fe3b185b49d4d219f5a0c1a20077380 2023-05-15T16:50:59+02:00 A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. Astridur Palsdottir Agnar Helgason Snaebjorn Palsson Hans Tomas Bjornsson Birkir Thor Bragason Solveig Gretarsdottir Unnur Thorsteinsdottir Elias Olafsson Kari Stefansson 2008-06-01T00:00:00Z https://doi.org/10.1371/journal.pgen.1000099 https://doaj.org/article/6fe3b185b49d4d219f5a0c1a20077380 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2409978?pdf=render https://doaj.org/toc/1553-7390 https://doaj.org/toc/1553-7404 1553-7390 1553-7404 doi:10.1371/journal.pgen.1000099 https://doaj.org/article/6fe3b185b49d4d219f5a0c1a20077380 PLoS Genetics, Vol 4, Iss 6, p e1000099 (2008) Genetics QH426-470 article 2008 ftdoajarticles https://doi.org/10.1371/journal.pgen.1000099 2022-12-30T21:16:14Z Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here, we report, based both on linkage disequilibrium and genealogical evidence, that all known copies of this mutation derive from a common ancestor born roughly 18 generations ago. Intriguingly, the genealogies reveal that obligate L68Q carriers born 1825 to 1900 experienced a drastic reduction in life span, from 65 years to the present-day average. At the same time, a parent-of-origin effect emerged, whereby maternal inheritance of the mutation was associated with a 9 year reduction in life span relative to paternal inheritance. As these trends can be observed in several different extended families, many generations after the mutational event, it seems likely that some environmental factor is responsible, perhaps linked to radical changes in the life-style of Icelanders during this period. A mutation with such radically different phenotypic effects in reaction to normal variation in human life-style not only opens the possibility of preventive strategies for HCCAA, but it may also provide novel insights into the complex relationship between genotype and environment in human disease. Article in Journal/Newspaper Iceland Directory of Open Access Journals: DOAJ Articles PLoS Genetics 4 6 e1000099 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
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language |
English |
topic |
Genetics QH426-470 |
spellingShingle |
Genetics QH426-470 Astridur Palsdottir Agnar Helgason Snaebjorn Palsson Hans Tomas Bjornsson Birkir Thor Bragason Solveig Gretarsdottir Unnur Thorsteinsdottir Elias Olafsson Kari Stefansson A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. |
topic_facet |
Genetics QH426-470 |
description |
Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here, we report, based both on linkage disequilibrium and genealogical evidence, that all known copies of this mutation derive from a common ancestor born roughly 18 generations ago. Intriguingly, the genealogies reveal that obligate L68Q carriers born 1825 to 1900 experienced a drastic reduction in life span, from 65 years to the present-day average. At the same time, a parent-of-origin effect emerged, whereby maternal inheritance of the mutation was associated with a 9 year reduction in life span relative to paternal inheritance. As these trends can be observed in several different extended families, many generations after the mutational event, it seems likely that some environmental factor is responsible, perhaps linked to radical changes in the life-style of Icelanders during this period. A mutation with such radically different phenotypic effects in reaction to normal variation in human life-style not only opens the possibility of preventive strategies for HCCAA, but it may also provide novel insights into the complex relationship between genotype and environment in human disease. |
format |
Article in Journal/Newspaper |
author |
Astridur Palsdottir Agnar Helgason Snaebjorn Palsson Hans Tomas Bjornsson Birkir Thor Bragason Solveig Gretarsdottir Unnur Thorsteinsdottir Elias Olafsson Kari Stefansson |
author_facet |
Astridur Palsdottir Agnar Helgason Snaebjorn Palsson Hans Tomas Bjornsson Birkir Thor Bragason Solveig Gretarsdottir Unnur Thorsteinsdottir Elias Olafsson Kari Stefansson |
author_sort |
Astridur Palsdottir |
title |
A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. |
title_short |
A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. |
title_full |
A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. |
title_fullStr |
A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. |
title_full_unstemmed |
A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries. |
title_sort |
drastic reduction in the life span of cystatin c l68q carriers due to life-style changes during the last two centuries. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2008 |
url |
https://doi.org/10.1371/journal.pgen.1000099 https://doaj.org/article/6fe3b185b49d4d219f5a0c1a20077380 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
PLoS Genetics, Vol 4, Iss 6, p e1000099 (2008) |
op_relation |
http://europepmc.org/articles/PMC2409978?pdf=render https://doaj.org/toc/1553-7390 https://doaj.org/toc/1553-7404 1553-7390 1553-7404 doi:10.1371/journal.pgen.1000099 https://doaj.org/article/6fe3b185b49d4d219f5a0c1a20077380 |
op_doi |
https://doi.org/10.1371/journal.pgen.1000099 |
container_title |
PLoS Genetics |
container_volume |
4 |
container_issue |
6 |
container_start_page |
e1000099 |
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