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Genetic Variation: Allelic
Variation
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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
Protein polymorphisms
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Electrophoretic variants
– Glucose-6-phosphate dehydrogenase
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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)
DNA polymorphisms
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RFLPs
– Co-dominant
– Due to single base changes, insertions or
deletions
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VNTRs (minisatellites)
– Probe detects repeat sequence (10-100 bp)
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Microsatellite markers (di- & tri-NT repeats)
– Probe detects flanking unique sequence
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SNPs
– Frequent and uniformly distributed in genome
– Identified by sequencing
Inheritance and segregation
analysis
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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)