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Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin.

Kapur S, Mehra S, Gajjar D, Vasavada A, Kapoor M, Sharad S, Alapure B, Rajkumar S - Indian J Ophthalmol (2009 May-Jun)

Bottom Line: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72.Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups.An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene.

View Article: PubMed Central - PubMed

Affiliation: Birla Institute of Technology and Science, Pilani - 333 031, Rajasthan, India. s_kapur@bits-pilani.ac.in

ABSTRACT

Aim: Polymorphisms in gamma-crystallins ( CRYG ) can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP)-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA / CRYGB genes in control subjects of western Indian origin.

Materials and methods: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes.

Results: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene.

Conclusions: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.

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Related in: MedlinePlus

Effect of T47C variation of CRYGB on transcription factor binding sites: Comparison between the most common 47C (a) and the rare allele 47T (b) for the putative transcription factor binding sites by AliBaba Version 2.1 software. The large dotted box shows the sites of alteration with corresponding transcription factors (small dotted box indicates sites of single nucleotide polymorphism and the transcription factors binding)
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Figure 0002: Effect of T47C variation of CRYGB on transcription factor binding sites: Comparison between the most common 47C (a) and the rare allele 47T (b) for the putative transcription factor binding sites by AliBaba Version 2.1 software. The large dotted box shows the sites of alteration with corresponding transcription factors (small dotted box indicates sites of single nucleotide polymorphism and the transcription factors binding)

Mentions: The sequence variation in CRYGB promoter region was also analyzed for change in transcription factor binding sites using the AliBaba software. While the sequence containing the “C” allele at nucleotide position 47 has binding sites for transcription factor ACE2 and PR, the substitution by “T” at this position results in the loss of both these binding sites [Fig. 2].


Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin.

Kapur S, Mehra S, Gajjar D, Vasavada A, Kapoor M, Sharad S, Alapure B, Rajkumar S - Indian J Ophthalmol (2009 May-Jun)

Effect of T47C variation of CRYGB on transcription factor binding sites: Comparison between the most common 47C (a) and the rare allele 47T (b) for the putative transcription factor binding sites by AliBaba Version 2.1 software. The large dotted box shows the sites of alteration with corresponding transcription factors (small dotted box indicates sites of single nucleotide polymorphism and the transcription factors binding)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2683433&req=5

Figure 0002: Effect of T47C variation of CRYGB on transcription factor binding sites: Comparison between the most common 47C (a) and the rare allele 47T (b) for the putative transcription factor binding sites by AliBaba Version 2.1 software. The large dotted box shows the sites of alteration with corresponding transcription factors (small dotted box indicates sites of single nucleotide polymorphism and the transcription factors binding)
Mentions: The sequence variation in CRYGB promoter region was also analyzed for change in transcription factor binding sites using the AliBaba software. While the sequence containing the “C” allele at nucleotide position 47 has binding sites for transcription factor ACE2 and PR, the substitution by “T” at this position results in the loss of both these binding sites [Fig. 2].

Bottom Line: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72.Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups.An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene.

View Article: PubMed Central - PubMed

Affiliation: Birla Institute of Technology and Science, Pilani - 333 031, Rajasthan, India. s_kapur@bits-pilani.ac.in

ABSTRACT

Aim: Polymorphisms in gamma-crystallins ( CRYG ) can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP)-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA / CRYGB genes in control subjects of western Indian origin.

Materials and methods: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes.

Results: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene.

Conclusions: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.

Show MeSH
Related in: MedlinePlus