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Next-generation sequencing of the mitochondrial genome and association with IgA nephropathy in a renal transplant population.

Douglas AP, Vance DR, Kenny EM, Morris DW, Maxwell AP, McKnight AJ - Sci Rep (2014)

Bottom Line: Kidneys are highly aerobic organs that are critically dependent on the normal functioning of mitochondria.Genetic variations disrupting mitochondrial function are associated with multifactorial disorders including kidney disease.This study sequenced the entire mitochondrial genome in a renal transplant cohort of 64 individuals, using next-generation sequencing, to evaluate the association of genetic variants with IgA nephropathy and end-stage renal disease (ESRD, n = 100).

View Article: PubMed Central - PubMed

Affiliation: Centre for Public Health, Queen's University Belfast, United Kingdom.

ABSTRACT
Kidneys are highly aerobic organs that are critically dependent on the normal functioning of mitochondria. Genetic variations disrupting mitochondrial function are associated with multifactorial disorders including kidney disease. This study sequenced the entire mitochondrial genome in a renal transplant cohort of 64 individuals, using next-generation sequencing, to evaluate the association of genetic variants with IgA nephropathy and end-stage renal disease (ESRD, n = 100).

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Related in: MedlinePlus

Vector NTI image of all SNPs on mitochondrial genome.All genes are named in black text, with protein coding genes indicated by orange arrows and ribosomal RNA genes indicated by green arrows. Top five most significantly associated SNPs shown labelled in dark red. Other significant SNPs represented by dark red lines, common SNPs by blue lines, and rare variants by black lines.
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f1: Vector NTI image of all SNPs on mitochondrial genome.All genes are named in black text, with protein coding genes indicated by orange arrows and ribosomal RNA genes indicated by green arrows. Top five most significantly associated SNPs shown labelled in dark red. Other significant SNPs represented by dark red lines, common SNPs by blue lines, and rare variants by black lines.

Mentions: A total of 427 differences from the reference sequence were identified (Figure 1, Supplementary Figure 2, Supplementary Table 2), of which 55 had a minor allele frequency (MAF) of zero, leaving 372 SNPs in this population; 113 SNPs had a MAF greater than 5%. Five common SNPs revealed evidence of significant association with ESRD where patients had a primary diagnosis of IgA nephropathy (Table 1; 6419A>C, P = 3.67 × 10−6; 199T>C, P = 3.00 × 10−4; 150C>T, P = 4.00 × 10−4; 8251G>A, P = 4.00 × 10−4; 16565C>G, P = 9.00 × 10−4). The association of 6419A>C was maintained following permutation testing (n = 100,000 permutations) based on 427 variants with resultant P = 0.01. Ten SNPs with MAF less than 5% and 65 common SNPs were present only in the case group of individuals with IgA nephropathy. Strong linkage disequilibrium was not observed (Figure 2).


Next-generation sequencing of the mitochondrial genome and association with IgA nephropathy in a renal transplant population.

Douglas AP, Vance DR, Kenny EM, Morris DW, Maxwell AP, McKnight AJ - Sci Rep (2014)

Vector NTI image of all SNPs on mitochondrial genome.All genes are named in black text, with protein coding genes indicated by orange arrows and ribosomal RNA genes indicated by green arrows. Top five most significantly associated SNPs shown labelled in dark red. Other significant SNPs represented by dark red lines, common SNPs by blue lines, and rare variants by black lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260226&req=5

f1: Vector NTI image of all SNPs on mitochondrial genome.All genes are named in black text, with protein coding genes indicated by orange arrows and ribosomal RNA genes indicated by green arrows. Top five most significantly associated SNPs shown labelled in dark red. Other significant SNPs represented by dark red lines, common SNPs by blue lines, and rare variants by black lines.
Mentions: A total of 427 differences from the reference sequence were identified (Figure 1, Supplementary Figure 2, Supplementary Table 2), of which 55 had a minor allele frequency (MAF) of zero, leaving 372 SNPs in this population; 113 SNPs had a MAF greater than 5%. Five common SNPs revealed evidence of significant association with ESRD where patients had a primary diagnosis of IgA nephropathy (Table 1; 6419A>C, P = 3.67 × 10−6; 199T>C, P = 3.00 × 10−4; 150C>T, P = 4.00 × 10−4; 8251G>A, P = 4.00 × 10−4; 16565C>G, P = 9.00 × 10−4). The association of 6419A>C was maintained following permutation testing (n = 100,000 permutations) based on 427 variants with resultant P = 0.01. Ten SNPs with MAF less than 5% and 65 common SNPs were present only in the case group of individuals with IgA nephropathy. Strong linkage disequilibrium was not observed (Figure 2).

Bottom Line: Kidneys are highly aerobic organs that are critically dependent on the normal functioning of mitochondria.Genetic variations disrupting mitochondrial function are associated with multifactorial disorders including kidney disease.This study sequenced the entire mitochondrial genome in a renal transplant cohort of 64 individuals, using next-generation sequencing, to evaluate the association of genetic variants with IgA nephropathy and end-stage renal disease (ESRD, n = 100).

View Article: PubMed Central - PubMed

Affiliation: Centre for Public Health, Queen's University Belfast, United Kingdom.

ABSTRACT
Kidneys are highly aerobic organs that are critically dependent on the normal functioning of mitochondria. Genetic variations disrupting mitochondrial function are associated with multifactorial disorders including kidney disease. This study sequenced the entire mitochondrial genome in a renal transplant cohort of 64 individuals, using next-generation sequencing, to evaluate the association of genetic variants with IgA nephropathy and end-stage renal disease (ESRD, n = 100).

Show MeSH
Related in: MedlinePlus