Increased instability of intermediate alleles in families with sporadic Huntington disease compared to similar sized intermediate alleles in the general population

Human Molecular Genetics
Y P GoldbergM R Hayden

Abstract

We have directly compared intergenerational stability of intermediate alleles (IAs) derived from new mutation families (IANM) for Huntington disease (HD) with IAs in the general population (IAGP) which occur in approximately 1 in 50 persons. Analysis of meiotic events in blood and sperm reveals that IANM are significantly more unstable than IAGP despite similar size. However, for both IANM and IAGP CAG changes were small and risks for inheriting an expansion into the HD affected range were low. Sequence analysis reveals that the CAG tract is generally interrupted by a penultimate CAA in IAGP, IANM and alleles in the affected range. In one new mutation family, however, two A-->G mutations result in a pure CAG tract which is associated with very marked instability. These mutations alter the predicted DNA hairpin structure with a predicted increase in the likelihood of large expansion, supporting the model that hairpin loop formation plays an important role in trinucleotide instability.

Citations

Aug 1, 1998·Movement Disorders : Official Journal of the Movement Disorder Society·E SilberD Saffer
Oct 1, 1995·Chromosoma·C T McMurray
Apr 5, 2000·Progress in Neurobiology·M LesortG V Johnson
Mar 10, 1998·Clinical Neurology and Neurosurgery·D E ShanZ A Wu
Jan 2, 2008·Cell Research·Irina V Kovtun, Cynthia T McMurray
Jan 21, 2011·European Journal of Human Genetics : EJHG·Simon C WarbyMichael R Hayden
Sep 20, 2012·European Journal of Human Genetics : EJHG·Monique LosekootUNKNOWN European Molecular Genetic Quality Network (EMQN)
Nov 5, 1997·Human Molecular Genetics·S E AndrewM R Hayden
May 1, 1997·Human Molecular Genetics·S M McNeilR H Myers
Sep 16, 1998·Human Molecular Genetics·G StevaninA Brice
Feb 26, 2004·Nucleic Acids Research·Michael J Dixon, Robert S Lahue
Aug 15, 2003·Molecular and Cellular Biology·Craig Spiro, Cynthia T McMurray
Jun 23, 2000·Journal of Neurology, Neurosurgery, and Psychiatry·S SieslingR A Roos
Feb 13, 2009·BMC Medical Genetics·Milena CannellaFerdinando Squitieri
Oct 31, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lora Bean, Pinar Bayrak-Toydemir
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·C T McMurray
Mar 5, 2015·American Journal of Medical Genetics. Part a·Wendy R UhlmannRoger L Albin
May 31, 2012·Clinical Genetics·R MacLeodUNKNOWN Editorial Committee and Working Group ‘Genetic Testing Counselling’ of the European Huntington Disease Network
Nov 17, 2004·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Milena CannellaFerdinando Squitieri
Aug 21, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·D BrocklebankUNKNOWN International-Venezuela Collaborative Research Group
Jun 27, 2008·Movement Disorders : Official Journal of the Movement Disorder Society·Wendy PhillipsRoger A Barker
May 21, 2009·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·A SemakaM R Hayden
Sep 17, 2013·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Alicia SemakaMichael R Hayden
Jan 29, 2013·Clinical Genetics·M C van RijE K Bijlsma
Mar 11, 2000·American Journal of Human Genetics·F Laccone, W Christian
Oct 23, 1997·American Journal of Human Genetics·E AlmqvistM R Hayden
Oct 6, 2014·Current Opinion in Genetics & Development·Do-Yup Lee, Cynthia T McMurray
Mar 3, 2009·American Journal of Human Genetics·Simon C WarbyMichael R Hayden
Dec 17, 2016·Journal of Huntington's Disease·Nancy R DowningUNKNOWN PREDICT-HD Investigators and Coordinators of the Huntington Study Group
Jan 24, 2017·Neurotoxicology·Ting-Kuang ChaoTamara Pringsheim
Dec 6, 2000·Arquivos de neuro-psiquiatria·S RaskinL A Andrade

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.