GENETIC ANALYSIS AND GENETIC DISEASES

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UNIT 3 GENETIC ANALYSIS AND GENETIC
DISEASES LECTURES 11. Alleles,
Recombination, and Linkage 12. Polymorphisms
and RFLPs 13. Positional Cloning and Gene
Mapping 14. DNA Sequence Analysis 15.
Molecular Basis of Genetic Diseases 16.
Oncogenes and Cancer 17. Developmental
Genetics (Dr. Peterson) 18. Transgenic
Models (Dr. Peterson) 19. Treatment of
Genetic Diseases (Dr. Peterson)
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11. Alleles, Recombination, and Linkage
a). Genetic loci and alleles b). Mitosis and
meiosis c). Recombination i). Meiotic
recombination ii). Effects of recombination on
chromosomes iii). Holliday model of
recombination d). Linkage i). Behavior of
alleles during meiosis ii). Linkage depends on
distance iii). Linkage of a chromosomal marker
to PKD1
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• Genetic loci and alleles
• definitions
• genetic locus a specific position or location
  on a chromosome
• allele one of the alternative versions of a DNA
  nucleotide
• sequence that may be at a given chromosomal
  locus
• diploid having maternal and paternal homologous
  chromosomes
• haploid having only one of the two homologous
  chromosomes
• homozygous having the same alleles at a genetic
  locus
• heterozygous having different alleles at a
  genetic locus

A
b
maternal chr. 1
a
b
paternal chr. 1
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(No Transcript)
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Meiosis I
Synapsis homologous chromosomes align
in pairs
2N
Maternal and paternal homologous chromosomes
Meiosis II
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Meiosis II
Four haploid (1N) gametes
1N
1N
1N
1N
Metaphase II
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• Genetic recombination and meiotic crossing over
• crossing over between homologous chromosomes in
  meiosis
• exchange of genetic information

The process of synapsis leads to crossing over
between homologs
Four different gametes
Cross-overs
Chromosomes after crossing over and exchange of
genetic information
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Four haploid (1N) gametes
1N
1N
1N
1N
Recombinant chromosomes are present in three of
the gametes in this case
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• effects of
• recombination
• on chromosomes
• within a family

• grandson inherits
• chromosome regions
• from all four of his
• grandparents
• chromosomes

• siblings inherit different chromosome
• regions from their parents

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• General Recombination or Homologous Recombination
• depends on sequence identity (or similarity)
• recombination is reciprocal
• Holliday model of genetic recombination

a)
e)
b)
f)
c)
d)
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1
2
f)
1
2
3
g)
4
3
4
12
1
1
2
2
h)
i)
cut
3
3
cut
4
4
j)
k)
Localized DNA exchange
Recombinant chromosomes
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• Linkage
• the tendency for loci close together on the same
  chromosome to
• be transmitted together through meiosis
• meiotic behavior of alleles at two loci

Parental
Linked loci (close or distant)
Unlinked loci
close on the same chromosome
distant on the same chromosome
separate chromosomes
A
a
A
a
A
a
B
b
B
b
B
b
recombinants
Gametes
A
a
A
a
a
A
a
A
a
b
B
b
B
b
B
b
B
b
25 25 25 25
50 50
non-recombinants
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• the strength of linkage depends on distance
• genetic distance
• one recombination unit is a Morgan
• a Morgan is the genetic distance over which one
  recombination
• event is observed per meiosis
• a centiMorgan (cM) is equal to 1 recombination
  frequency
• physical distance
• one cM is approximately 106 base pairs of DNA
• on average there are about 1-3 recombination
  events per
• chromosome per meiosis

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• linkage of the PKD1 (polycystic kidney disease)
  gene
• to locus 2 but not locus 1
• (locus 1 is too far away on the same chromosome
  to show linkage)

a
A
Locus 1
B
PKD1
b (wild type)
c
C
Locus 2
A
A
a
A
a
B
b
b
b
B
C
c
c
c
C
(only the paternal chromosomes are shown)
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• Learning objectives
• know what alleles are and how they are expressed
• know how alleles segregate during mitosis and
  meiosis
• understand the effect of meiotic crossing over
  on the
• segregation of genetic loci
• understand the mechanism of homologous
  recombination
• understand what the term linkage means and the
  relationship
• between linkage and distance along a chromosome