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GENETICS REFRESHER (TYPES OF DNA CHANGES THAT CAUSE GENETIC DISEASES…
GENETICS REFRESHER
VARIATION OF GENE TRANSMISSION AND EXPRESSION
Allelic Heterogeneity: similar phenotype due to different mutation in same gene (Ex: Beta-thalassemia)
Variety of mutations:
Promoter region
Abnormal RNA splicing
Coding regions
Silent, nonsense (stop codon), missense, framshift
Locus Heterogeneity: same phenotype due to mutations in different genes (Ex: OI)
INHERITANCE OF GENES
Mendelian: Autosomal, X-linked, Y-linked
Non-Mendelian: mitochondrial
AUTOSOMAL RECESSIVE INHERITANCE
Parents and children of affected person are obligate carriers
TYPES OF DNA CHANGES THAT CAUSE GENETIC DISEASES
Germline mutations: changes in DNA that are passed on to offspring, Somatic mutations are not
Small changes at lvl of nucleotides
Transition: one purine for another purine or one pyrimidine for another pyrimidine
Transversion: purine for a pyrimidine
Changes within protein coding sequence
Point Mutations
Silent: single base substitution but no change in AA sequence
Missense: change in AA sequence
Nonsense: change to stop codon
Frameshift: addition or deletion of 1-2 nucleotides (or more) results in misreading subsequent codons and usu results in a truncated protein
Changes in DNA > major deletions/insertions > small or single base pair changes
DNA-sequencing determines actual nucleotide sequence
Sequencing variants: pathogenic, benign, variant of unknown significance, incidental findings
Sequence-tagged site is a unique DNA sequence with a known location, can be detected by PCR and serve as landmarks for mapping
PCR used to amplify DNA which can then be visualized on a gel or sequenced
Multiplex PCR: multiple primers used that cover different regions of the gene and produce PCR products of different sizes in one reaction. Lack of a PCR product indicates a deletion in the genomic DNA
Types of polymorphisms
SNPs (single nucleotide polymorphism): usu but not always results in no change in AA sequence; detected by PCR followed by gel electrophoresis
STRs (short tandem repeats)
VNTR (variable number tandem repeats): highly polymorphic, inherited in strict Mendelian fashion; useful in linkage studies due to greater chance that an individual is heterozygous for a perticular marker
Linkage Studies
Linkage: when 2 loci (genes) are located close enough on the same chromosome that their recombination frequency is less than 50%
Recombination frequency: probability of recombination b/t 2 loci; >50% means not linked and the genes behave as if they were on separate chromosomes