Limits...
Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) Founder Mutation: Clues from Haplotyping of Short Tandem Repeats on Chromosome 17p.

Paskulin DD, Giacomazzi J, Achatz MI, Costa S, Reis RM, Hainaut P, dos Santos SE, Ashton-Prolla P - PLoS ONE (2015)

Bottom Line: A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil.So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin.Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.

View Article: PubMed Central - PubMed

Affiliation: Post-Graduate Program, Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

ABSTRACT
Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial history. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Iberic origin, distant in about 72-84 generations (2000 years assuming a 25 years intergenerational distance) and thus pre-dating European migration to Brazil. So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.

Show MeSH

Related in: MedlinePlus

Brazilian Population Growth between 1550–2000.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664269&req=5

pone.0143262.g003: Brazilian Population Growth between 1550–2000.

Mentions: Our estimate for the age of the mutation should be considered with caution. First, because absolutely precise population growth rates for the last 500 years in Brazil cannot be established, and we have used, as have many others, an estimate of this growth (Fig 3). Second, an apparent generation distance of 72–84 generations, amounting to about 2000 years, implies that the mutation has arisen in an ancestor living about 1,500 years before the arrival of the first Portuguese-Iberic settlers in Latin America. Furthermore, the fact that this 2000-year haplotype diversity is observed among Brazilians themselves implies that the current population of Brazilian p.Arg337His carriers originated from several distantly related ancestors who where separated by at least 50 generations (about 1000 years) at the time of their arrival on the Latin American continent. Indeed, assuming a 2000-years old history for the p.Arg337His haplotype, its geographic spread in Brazil cannot have taken place before the early 18th to mid-19th century, when the first large waves of migrants of Europeans settled in Southern Brazil. Finally, if the mutation is indeed European in origin, one would expect to observe it at more significant frequencies in European LFS/LFL families. Thus, a more detailed analysis of the common ancestry of p.Arg337His carriers, and perhaps an extended mutation search in other populations may be needed to understand the historical geographical spread of this alteration.


Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) Founder Mutation: Clues from Haplotyping of Short Tandem Repeats on Chromosome 17p.

Paskulin DD, Giacomazzi J, Achatz MI, Costa S, Reis RM, Hainaut P, dos Santos SE, Ashton-Prolla P - PLoS ONE (2015)

Brazilian Population Growth between 1550–2000.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664269&req=5

pone.0143262.g003: Brazilian Population Growth between 1550–2000.
Mentions: Our estimate for the age of the mutation should be considered with caution. First, because absolutely precise population growth rates for the last 500 years in Brazil cannot be established, and we have used, as have many others, an estimate of this growth (Fig 3). Second, an apparent generation distance of 72–84 generations, amounting to about 2000 years, implies that the mutation has arisen in an ancestor living about 1,500 years before the arrival of the first Portuguese-Iberic settlers in Latin America. Furthermore, the fact that this 2000-year haplotype diversity is observed among Brazilians themselves implies that the current population of Brazilian p.Arg337His carriers originated from several distantly related ancestors who where separated by at least 50 generations (about 1000 years) at the time of their arrival on the Latin American continent. Indeed, assuming a 2000-years old history for the p.Arg337His haplotype, its geographic spread in Brazil cannot have taken place before the early 18th to mid-19th century, when the first large waves of migrants of Europeans settled in Southern Brazil. Finally, if the mutation is indeed European in origin, one would expect to observe it at more significant frequencies in European LFS/LFL families. Thus, a more detailed analysis of the common ancestry of p.Arg337His carriers, and perhaps an extended mutation search in other populations may be needed to understand the historical geographical spread of this alteration.

Bottom Line: A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil.So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin.Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.

View Article: PubMed Central - PubMed

Affiliation: Post-Graduate Program, Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

ABSTRACT
Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial history. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Iberic origin, distant in about 72-84 generations (2000 years assuming a 25 years intergenerational distance) and thus pre-dating European migration to Brazil. So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.

Show MeSH
Related in: MedlinePlus