Chapter title |
A Founder Effect for the HGD G360R Mutation in Italy: Implications for a Regional Screening of Alkaptonuria.
|
---|---|
Chapter number | 534 |
Book title |
JIMD Reports, Volume 30
|
Published in |
JIMD Reports, January 2016
|
DOI | 10.1007/8904_2016_534 |
Pubmed ID | |
Book ISBNs |
978-3-66-253680-3, 978-3-66-253681-0
|
Authors |
Berardino Porfirio, Roberta Sestini, Greta Gorelli, Miriam Cordovana, Alessandro Mannoni, Jeanette L. Usher, Wendy J. Introne, William A. Gahl, Thierry Vilboux, Porfirio, Berardino, Sestini, Roberta, Gorelli, Greta, Cordovana, Miriam, Mannoni, Alessandro, Usher, Jeanette L., Introne, Wendy J., Gahl, William A., Vilboux, Thierry |
Abstract |
We sought to establish rapid and specific genotyping methods for G360R mutation and for seven tightly linked markers in the homogentisate dioxygenase gene to address the question of whether G360R is a mutational hot spot or the result of a founder effect, as it has been repeatedly found in alkaptonuric patients from a geographic isolate in Italy.For G360R and single nucleotide polymorphism genotyping, high-resolution melting analysis was performed. Microsatellites were analysed by multiplex PCR and capillary electrophoresis. To investigate the natural history of the G360R mutation, we genotyped markers in 52 controls and in 8 unrelated patients from the UK and USA, who also segregated the G360R mutation, and calculated its age using DMLE+2.3 software.A distinct G360R-bearing haplotype was identified in all patients of Caucasian descent. Estimated mutation age was 545 generations (95% credible set, 402-854), suggesting that G360R arose in an ancestor who lived 8,000-10,000 years BC. Archaeological, historical and demographic data support that a G360R carrier has settled the remote valley where present-day population might have a heterozygote frequency of at least 6%.Given the late health-threatening complications of alkaptonuria and a cure within reach, inhabitants of this isolate would benefit from screening and genetic counselling. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 50% |
United States | 1 | 25% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 7 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 2 | 29% |
Student > Ph. D. Student | 1 | 14% |
Professor > Associate Professor | 1 | 14% |
Student > Master | 1 | 14% |
Unknown | 2 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 3 | 43% |
Agricultural and Biological Sciences | 1 | 14% |
Biochemistry, Genetics and Molecular Biology | 1 | 14% |
Unknown | 2 | 29% |