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Transcript
Linkage, Recombination and Eukaryotic Mapping Part 2 Outline • Gene mapping in Humans – Pedigrees and linkage • Physical Chromosome mapping Nail-Patella Syndrome – Autosomal dominant: abnormal fingernails and absent (underdeveloped kneecaps) – ABO blood type alleles linkage (2 out of 13 offspring) 2/13= 0.154 recombination frequency Physical Chromosome Mapping • Provides us alternative methods for gene mapping that do not rely on rates of crossing over to determine gene location Methods that are considered “physical mapping of the chromosome” • Deletion mapping • Somatic Cell hybridization • In Situ Hybridization • DNA Sequencing DELETION MAPPING (this has been used to map Muscular Dystrophy gene to X chromosome 50% have mutation all have normal phenotype Deletion Mapping • Can also be done with homozygous recessive Crossed with • Homozygous wt+ but with deletion(s) Offspring will be: B+ Deletion area a b B+ a b aB+ a b We now know this deletion includes the locus that is within the region deleted for A+ but not for B+ You can perform this a panel of deletions. Mutations del a 1 m 2 m 3 + 4 + 5 + 6 + a b + + m + + m c m + m m + + d + + m m m m e + + m m m + f m + + + + + d c etc. chromosome deletion 1 deletion 2 deletion 3 deletion 4 deletion 5 deletion 6 f? a f? c e d b SOMATIC CELL HYBRIDIZATION + Human somatic cell You set up a panel of these hybrid cells that include a random selection of human chromosomes Look for which cell lines produce the product AND which chromosomes are present. Bingo! You can determine which gene is associated with which chromosome! In Situ Hybridization detects genes on chromsomes DNA SEQUENCING More to come with our molecular discussions Practice Physical Mapping • Questions 4, 5, 26 and 27 at the back of chapter 7 to try out your skills at deletion analysis and somatic-cell hybridization. • I will post the answer for question 26 (others are in the book). • Does not have to be handed in—just to practice to see if it all makes sense. The End
