USMLE Step 1 Web Prep — Gene Mapping and Cloning
386075 >>> 00:00:00
SLIDE 1 of 13
Chapter 4
Gene Mapping and Cloning
386080 >>> 00:00:45
SLIDE 2 of 13
Gene Mapping: Linkage Analysis
Determining:
Where a gene is located
How far apart two genes are
Syntenic loci - on the same chromosome
Linked loci - close enough together so that chance of recombination is less
than 50%
o
o


386085 >>> 00:03:56
SLIDE 3 of 13
Gene Mapping: Linkage Analysis
Importance:
Cloning Genes
Genetic Diagnostic Tests
386090 >>> 00:05:20
SLIDE 4 of 13
386095 >>> 00:12:53
SLIDE 5 of 13
386100 >>> 00:18:37
SLIDE 6 of 13
386105 >>> 00:25:19
SLIDE 7 of 13
Recombination Frequency
In our example: 1/6 = 17%
 Provides measure of genetic distance between linked loci
 One centimorgan = 1% recombination
 One centimorgan = 1 million base pairs
386110 >>> 00:28:55
SLIDE 8 of 13
LOD (Log of Odds) Scores
LOD = log10 P (recombination frequency = θ)
P(recombination frequency of 50%)
LOD score greater than 3 means loci are linked
LOD less than -2 means there is no linkage
386115 >>> 00:29:42
SLIDE 9 of 13
How could the USMLE test your understanding of LOD scores?
Interpret the following table of LOD scores and recombination
frequencies (θ):
θ
LOD
0.0
-inf
0.5
1.7
0.1
3.5
0.2
2.8
0.3
2.2
0.4
1.1
0.5
0.0
The highest LOD score is at a recombination frequency of 10%, so the
two loci are most likely to be 10 cM apart.
386120 >>> 00:34:00
SLIDE 10 of 13
Linkage Disequilibrium
 Specific alleles at two linked loci are observed together as a haplotype more (or
less) frequently than predicted by chance alone
 The greater the linkage disequilibrium, the more closely linked the loci
386125 >>> 00:36:56
SLIDE 11 of 13
386130 >>> 00:42:12
SLIDE 12 of 13
386135 >>> 00:51:52
SLIDE 13 of 13
Gene Cloning
 Find linkage to a known marker
 Identify protein-coding regions
 Compare DNA sequences of these genes in affected and unaffected individuals