SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia
Abstract
:1. Introduction
2. Case Presentation
3. Molecular Studies
3.1. SNP Analysis
3.2. WES
3.3. Primer Design and Sanger-based Sequencing
4. Results
Chromosome | Cytoband | Chromosome Coordinates (hg18) | Size (kb) | ||
---|---|---|---|---|---|
Start | End | Start | End | ||
4 | q13.3 | q22.2 | 75,140,321 | 94,467,450 | 19,327 |
8 | q12.2 | q21.1 | 62,360,831 | 82,468,093 | 20,107 |
11 | q13.3 | q14.1 | 70,171,744 | 83,268,529 | 13,097 |
13 | q12.11 | q12.3 | 21,382,994 | 28,897,752 | 7,515 |
13 | q22.3 | q32.3 | 77,509,929 | 100,244,550 | 22,735 |
18 | q11.1 | q11.2 | 16,803,434 | 23,248,050 | 6,445 |
Total | - | - | - | - | 89,226 |
Gene | Phenotype | Inheritance |
---|---|---|
COQ2 | Multiple-system atrophy | AR, AD |
GRID2 | Autosomal recessive spinocerebellar ataxia-18 | AR |
TTPA | Ataxia with isolated vitamin E deficiency | AR |
CYP7B1 | Autosomal recessive spastic paraplegia-5A | AR |
PEX2 | Peroxisome biogenesis disorder-5B | AR |
SACS | Autosomal recessive spastic ataxia of Charlevoix-Saguenay | AR |
ATP8A2 | Cerebellar ataxia, mental retardation, and disequilibrium syndrome-4 | AR |
Gene | Nucleotide Change | Amino Acid Change | Variant State | Located in a Region of LCSH Common to Both Affected Siblings | MAF * | Comments |
---|---|---|---|---|---|---|
CACNA1A | NM_023035.2: c.793C>G | NP_075461.2: p.(Gln265Glu) | Het | No | 0.0 | Point mutations in CACNA1A are consistent with phenotype. Doesn’t fit apparent inheritance pattern in this pedigree. |
SACS | NM_014363.4: c.7962T>G | NP_003045.2: p.(Tyr2654*) | Hom | Yes | 0.0 | Truncating mutation. Homozygous in both affected siblings. Consistent with phenotype. |
ZNF592 | NM_014630.2: c.3023G>A | NP_055445.2: p.(Arg1008Gln) | Het | No | 4.523 × 10−5 | Incomplete concordance with phenotype; AR disorder, single het variant detected only. |
5. Discussion
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Nickerson, S.L.; Marquis-Nicholson, R.; Claxton, K.; Ashton, F.; Leong, I.U.S.; Prosser, D.O.; Love, J.M.; George, A.M.; Taylor, G.; Wilson, C.; et al. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia. Microarrays 2015, 4, 490-502. https://doi.org/10.3390/microarrays4040490
Nickerson SL, Marquis-Nicholson R, Claxton K, Ashton F, Leong IUS, Prosser DO, Love JM, George AM, Taylor G, Wilson C, et al. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia. Microarrays. 2015; 4(4):490-502. https://doi.org/10.3390/microarrays4040490
Chicago/Turabian StyleNickerson, Sarah L., Renate Marquis-Nicholson, Karen Claxton, Fern Ashton, Ivone U. S. Leong, Debra O. Prosser, Jennifer M. Love, Alice M. George, Graham Taylor, Callum Wilson, and et al. 2015. "SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia" Microarrays 4, no. 4: 490-502. https://doi.org/10.3390/microarrays4040490