Genetic Variation: Allelic Variation

1
Genetic Variation Allelic Variation

• Polymorphism - allelic variation - is essential
  to
• Study inheritance patterns
• Map phenotypes and anchor genes to the genetic
  map by co-segregation analysis
• Genetically determined variability among humans
  is due to a difference in 0.1 of the genomic
  sequence!
• Polymorphisms are exhibited at levels of
• Morphology
• Protein
• DNA

2
Protein polymorphisms

• Electrophoretic variants
• Glucose-6-phosphate dehydrogenase
• ABO system of blood cell antigens
• 3 alleles of glycosyl-transferase that adds
  glycosyl group to H antigen
• A - enzyme recognizes N-acetylgalactosamine
• B - enzyme recognizes D-galactose
• O - enzyme lacks transferase activity
• A and B are co-dominant O is recessive
• 4 phenotypes A (A/A A/O), B (B/B B/O), AB
  (A/B), O (O/O)

3
DNA polymorphisms

• RFLPs
• Co-dominant
• Due to single base changes, insertions or
  deletions
• VNTRs (minisatellites)
• Probe detects repeat sequence (10-100 bp)
• Microsatellite markers (di- tri-NT repeats)
• Probe detects flanking unique sequence
• SNPs
• Frequent and uniformly distributed in genome
• Identified by sequencing

4
Inheritance and segregation analysis

• Follow phenotypes in families
• Morphology or protein or DNA
• Must assess in each individual
• Morphology or disease
• Protein variants (electrophoretic gels)
• DNA polymorphisms
• Southern blotting (RFLPs, VNTRs)
• PCR and electrophoresis (microsatellites)
• Sequence analysis (DNA chips, other)