第八章基因突变解读.ppt

* CPD – cyclobutane pyrimidine dimer photolyase; Many organisms don’t have this light-dependent repair by photolyases (humans?). * * UvrC has the endonuclease activity; UvrA and B bind to the damaged site. NER can also repair other types of DNA damage. Essential in humans; people with Xeroderma pigmentosum have reduced NER extreme UV sensitivity. Also, a NER deficiency in humans promotes cancer. Probably a minor pathway for dimer repair in organisms with photolyases. * DNA glycosylase cuts the bond between base and sugar. AP refers to Apurinic or Apyrimidinic nuclease. * * Dam methylase is delayed for about 10 min, then it methylates the new replicon. Case 1 Analysis 147D Candidate SNPs Found by NGS: Gene Transcript ID Exon cDNA Protein Position heterozygosity Depth TTN NM_001267550 exon328 c.C87158T p.T29053I chr2- 179422923 het 215/174(0.45) TTN NM_001267550 exon266 c.G49967A p.R16656H chr2- 179477285 het 172/176(0.51) TTN NM_001267550 exon125 c.G32062C p.V10688L chr2- 179553813 het 115/108(0.48) SGCG NM_000231 exon4 c.C320T p.S107L chr13-het 224/204(0.48) SGCG NM_000231 exon8 c.G787A p.E263K chr13het 196/149(0.43) SNPs in SGCG match clinical phenotype Case 1 Analysis SNP info SGCG chr13NM_000231 exon8 Patient 147D Allele1 GCCTCTACGAAATCTG 　 C.G787A p.E263K het Allele2 GCCTCTACAAAATCTG Patient’s Mother 157D Allele1 GCCTCTACGAAATCTG 　 C.G787A p.E263K het Allele2 GCCTCTACAAAATCTG Patient’s father 175D Allele1 CCTCTACGAAATCTG 　 Normal hom Allele2 CCTCTACGAAATCTG SNP info SGCG chr13NM_000231 exon4 Patient 147D Allele1 ACAATCAACCCAGAAT 　 c.C320T p.S107L het Allele2 ACAATTAACCCAGAAT Patient’s Mother 157D Allele1 ACAATCAACCCAGAAT 　 Normal hom Allele2 ACAATCAACCCAGAAT Patient’s father 175D Allele1 CTACAATCAACCCAG 　 C.C320T p.S107L het Allele2 CTACAATTAACCCAG Validation By Sequencing Case 2 Analysis 103D Candidate SNPs Found by NGS: Gene Transcript ID Exon cDNA Protein Position heterozygosity Depth T