Limits...
Frequency of HNF4A-P.I463V Variant in the Tunisian North-African Population and Its Relation with Diabetes Mellitus.

Amara A, Ben Charfeddine I, Ghédir H, Mamaï O, Jemni-Yacoub S, Chaieb L, Saad A, Chadli-Chaieb M, Gribaa M - Iran. J. Public Health (2015)

Bottom Line: We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population.It is also present in different ethnicities and in- silico analysis showed conflicting results.

View Article: PubMed Central - PubMed

Affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia ; Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.

ABSTRACT

Background: HNF4A-p.I463Vvariant, reported previously in two distinct families suspected of MODY-1, is assessed in this report to determine whether it is a mutation or a polymorphism (frequency >1%).

Methods: 200 Tunisian healthy people were screened for the presence of HNF4A-p.I463V variant, using RFLP-PCR technique and sequencing. Then, the frequency of this variant was estimated in the Tunisian population and compared to other populations registered in genetic databases. We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.

Results: HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population. PolyPhen2 predicted that it is a polymorphism, whereas mutation T@sting suggested a probably affected mutant protein.

Conclusion: HNF4A-p.I463V has a relatively high frequency (>1%) in our control cohort. It is also present in different ethnicities and in- silico analysis showed conflicting results. For these reasons, HNF4A-p.I463V should not be considered as a mutation responsible for MODY-1.

No MeSH data available.


Isoleucine amino-acid in position 463 is conserved across species A portion of HNF4A exon 10 amino-acid sequence is compared between various species. The human Isoleucine at codon 463 and Isoleucine of other species are framed in a red box. The species are annotated in bold and the NCBI accession numbers in blue
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4402419&req=5

Figure 3: Isoleucine amino-acid in position 463 is conserved across species A portion of HNF4A exon 10 amino-acid sequence is compared between various species. The human Isoleucine at codon 463 and Isoleucine of other species are framed in a red box. The species are annotated in bold and the NCBI accession numbers in blue

Mentions: This variant occurs in a conserved region across species (PhyloP score = 4.56 [−14.1; 6.4]) and is localized in the F domain of HNF4A (Fig. 3). This domain plays a role in the protein transactivation activity (17).


Frequency of HNF4A-P.I463V Variant in the Tunisian North-African Population and Its Relation with Diabetes Mellitus.

Amara A, Ben Charfeddine I, Ghédir H, Mamaï O, Jemni-Yacoub S, Chaieb L, Saad A, Chadli-Chaieb M, Gribaa M - Iran. J. Public Health (2015)

Isoleucine amino-acid in position 463 is conserved across species A portion of HNF4A exon 10 amino-acid sequence is compared between various species. The human Isoleucine at codon 463 and Isoleucine of other species are framed in a red box. The species are annotated in bold and the NCBI accession numbers in blue
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402419&req=5

Figure 3: Isoleucine amino-acid in position 463 is conserved across species A portion of HNF4A exon 10 amino-acid sequence is compared between various species. The human Isoleucine at codon 463 and Isoleucine of other species are framed in a red box. The species are annotated in bold and the NCBI accession numbers in blue
Mentions: This variant occurs in a conserved region across species (PhyloP score = 4.56 [−14.1; 6.4]) and is localized in the F domain of HNF4A (Fig. 3). This domain plays a role in the protein transactivation activity (17).

Bottom Line: We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population.It is also present in different ethnicities and in- silico analysis showed conflicting results.

View Article: PubMed Central - PubMed

Affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia ; Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.

ABSTRACT

Background: HNF4A-p.I463Vvariant, reported previously in two distinct families suspected of MODY-1, is assessed in this report to determine whether it is a mutation or a polymorphism (frequency >1%).

Methods: 200 Tunisian healthy people were screened for the presence of HNF4A-p.I463V variant, using RFLP-PCR technique and sequencing. Then, the frequency of this variant was estimated in the Tunisian population and compared to other populations registered in genetic databases. We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.

Results: HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population. PolyPhen2 predicted that it is a polymorphism, whereas mutation T@sting suggested a probably affected mutant protein.

Conclusion: HNF4A-p.I463V has a relatively high frequency (>1%) in our control cohort. It is also present in different ethnicities and in- silico analysis showed conflicting results. For these reasons, HNF4A-p.I463V should not be considered as a mutation responsible for MODY-1.

No MeSH data available.