ANNOUNCEMENTS

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ANNOUNCEMENTS

• Exam 1 is Friday. Take-home 1 is due at Exam 1.
• Check the missing iClicker list on web page...

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The discovery of D4S10, an anonymous DNA marker
genetically linked to Huntingtons disease,
introduced the capacity for presympotomatic
diagnosis in this late-onset neurodegenerative
disorder and raised the hope of cloning and
characterizing the defect based on its
chromosomal location.
D4S10 H
5
3
100 D
110 d
X
5
120 d
140 d
100 ?
110 d
What is the probability that this child will
develop Huntingtons?
Remember, these two loci are 5 cM apart.
(a) 0(b) 0.05(c) 0.50(d) 0.95(e) 1.00
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100 D
110 d
X
5
120 d
140 d
100 ?
110 d
What is the probability that this child will
develop Huntingtons?
Remember, these two loci are 5 cM apart.
(a) 0(b) 0.05(c) 0.50(d) 0.95(e) 1.00
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Linkage maps can be lined up with cytological
maps of chromosome features and physical maps of
the DNA sequence.
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• Human Genome
• 23 chromosomes (cytological map)
• 2.9 billion basepairs (physical map)
• 3,550 cM (linkage map)
• Sex differences in recombination rates
• Females - map length 4,510 cM
• Males - map length 2,560 cM (57)

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Banding pattern during metaphase
Banding pattern during prophase
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How can we put mapped genes on chromosomes??
FISH (fluorescence in situ hybridization)
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200 cM (in women) 1 cM 1 recombination
Most genes on this chromosome are syntenic but
unlinked
Human chromosomes
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Sequence map
Annotated, sequence-based map of an 8-mb segment
of DNA at the tip of human chromosome 1.
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Applications of human genome mapping Diagnostic
Huntingtons BRCA1 and BRCA2 Diabetes 2,
and many more Therapeutic Functional basis of
disease (esp. complex diseases) Pharmacogenomics

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Scientists Unmask Genetic Markers Associated With
Psoriasis -ScienceDaily (Jan. 27, 2009)
Scientists at the University of Michigan have
found DNA "hotspots" that may reveal how genetic
differences among individuals result in
psoriasis, an autoimmune disease of the skin.
Published in Nature Genetics, the findings could
lead to new drug targets and tailored treatments
for the disease. Psoriasis affects some 7.5
million people in the United Statesbetween 10
and 30 percent of patients develop psoriatic
arthritis, a painful inflammation of the joints.
Psoriasis has a strong genetic component...But
the genes responsible for psoriasis haven't yet
been completely understood...Researchers used
cutting-edge genomic technology to identify
subtle genetic signals influencing the risk of
psoriasis(and) increased the number of
independent genetic "hotspots," or loci,
confidently associated with psoriasis from one to
10. The team looked for single nucleotide
polymorphisms (SNPs), or DNA changes, at 438,670
sites in 1,359 psoriasis cases and 1,400 healthy
controls.
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Evans, W. E., and M. V. Relling. 1999. Science
286487-491.
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Next Chromosomal variation

• These socks belong to a
• boy
• girl

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Muntjac karyotypes
Indian Muntjac (2N 46)
Reeves Muntjac (2N 8)
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Muntjac karyotypes

• Which muntjac species has more genes?
• Indian
• Reeves
• Neither, they have basically the same number and
  kind of genes

Indian Muntjac (2N 46)
Reeves Muntjac (2N 8)
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Chromosomal variation

• Variation in chromosome number
• Aneuploidy
• Euploidy/Polyploidy
• Variation in chromosome structure
• Change in the amount of genetic information
• - deletions
• - duplications
• Rearrangement of gene locations
• - inversions
• - translocations

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Variation in chromosome number
Ploidy - refers to the number of sets of
chromosomes an individual possesses (e.g.,
diploid, tetraploid) Aneuploidy - loss or gain
of an entire chromosome (i.e., N 1 or 3 for 1
chromosome, 2 for others) Euploidy - true
ploidy, means an individual has equal s of all
chromosomes (not aneuploid) Polyploidy - a
general term for ploidy gt 2N
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Chromosome composition
Normal fruit fly
1(x)
2
3
4
Diploid 2n (2 sets)
Polyploid fruit flies
Aneuploid fruit flies
Triploid 3n (3 sets)
Trisomy 2 (2n 1)
Tetraploid 4n (4 sets)
Monosomy 1 (2n 1)

Variations in euploidy
Variations in aneuploidy
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Chromosomal abnormalities are common in humans
Trisomies
28 of clinically recognized pregnancies
4 of clinically recognized pregnancies
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Most trisomies result from nondisjunction during
female meiosis I or II.
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Meiotic timeline in humans
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Meiotic nondisjunction and the origin of Down
syndrome.
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Anueploidy produces imbalances in the amount of
gene products
In most cases, these individuals will have
developmental abnormalities relative to a euploid
individual
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Karyotype of a female with Down syndrome.
Trisomy-21
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1/700 births
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Aneuploidy of sex chromosomes is not as harmful

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Why are no trisomies for the larger autosomal
chromosomes detected at birth?
Frequency
Differential survivalTrisomies for larger
autosomes die shortly after fertilization.
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Frequency
Why are sex chromosome abnormalities so much more
common than autosomal abnormalities?
X-inactivation reduces the harmful effects of
aneuploidy for the X chromosome.
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Why are males normal? That is, males have only
one-half of the copy number of X-linked genes
that female do. Development in mammals is very
sensitive to an imbalance in the number of genes.
Too much or too little gene product generally
results in abnormal phenotypes. ANSWER One of
the X-chromosomes is inactivated in human
(mammalian) females.
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Table 7.1
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X-chromosome inactivation
Somatic mosiac
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• Polyploidy (more than 2 sets of chromosomes)
• Polyploidy is common in plants, occasional in
  fish and amphibians, and rare in mammals
• Polyploidy is thought to be important over
  evolutionary history, since whole genome
  duplications may provide raw material for
  adaptation
• Odd ploidies (3N) are often sterile, but even
  ploidies (4N, etc.) are fertile and often highly
  fit

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Polyploidy

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Diploid Tetraploid Hyla These are essentially
the same frog - it is the balance between the
number of gene copies that is important for
proper development, not necessarily the total
number of gene copies
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Chromosomal variation

• Variation in chromosome number
• Aneuploidy
• Euploidy/Polyploidy
• Variation in chromosome structure
• Change in the amount of genetic information
• - deletions
• - duplications
• 2. Rearrangement of gene locations
• - inversions
• - translocations