Linking chromosomes to genetics

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Welcome back to IB 150...
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What is the highest percent recombination that
can be measured in a dihybrid testcross?
The highest percent recombination that can be
measured is 50. This is the same value as in
the case of independent assortment. If two genes
are very far apart, they will be inherited as if
they were on different chromosomes - even if they
are truly on the same chromosome. This is
because almost every meioisis will have a
crossover between the pair of genes.
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b
a
b
a
a
b
a
b
Cell 1
Cell 1
A
B
A
B
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B
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b
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b
a
a
b
b
a
Cell 2
Cell 2
A
B
B
A
A
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A
b
a
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a
b
Cell 3
Cell 3
A
B
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A
Genes a and b far apart
Genes a and b close
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But what about multiple crossovers?
centromere
Chiasmata (2 of them) in meiosis in a salamander.

Fig. 13.11 (similar)
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a
b
Even multiple crossovers produce 1/2 parental
gametes, and 1/2 recombinant gametes.
b
a
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B
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a
b
b
a
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What is the highest percent recombination that
can be measured in a dihybrid testcross?
The highest percent recombination that can be
measured is 50. This is the same value as in
the case of independent assortment. If two genes
are very far apart, they will be inherited as if
they were on different chromosomes - even if they
are truly on the same chromosome.
Genes that are on the same physical chromosome
are said to be syntenic (on the same thread),
even if they are so far apart that they show
independent assortment.
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The percent recombination value is used a a
recombinational map distance in genetics.
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The percent recombination value is used a
recombinational map distance in genetics.
But is is transformed so it is not written
exactly as a percentage. We use a unit called a
centiMorgan, or cM. One percent recombination is
1 cM. Thus 50 recombination equates to a map
distance of 50cM.
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• Fig. 15.7. Sturtevant used the test cross design
  to map the relative position of three fruit fly
  genes, body color (b), wing size (vg), and eye
  color (cn). He found that by making all possible
  dihybrid crosses, he could deduce the gene order.
• The recombination frequency between cn and b is
  9.
• The recombination frequency between cn and vg is
  9.5.
• The recombination frequency between b and vg is
  17.
• The only possible arrangement of these three
  genes places the eye color gene between the
  other two.

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Fig. 15.7. But why is 17 a little less than 9
9.5 18.5? Sturtevant found the answer by
making trihybrid crosses and looking carefully at
all possible progeny.
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Why dont the numbers add up?

• The three recombination frequencies in our
  mapping example are not quite additive 9 (b-cn)
  9.5 (cn-vg) gt 17 (b-vg).
• This results from multiple crossing-over events.
• A second crossing-over cancels out the first
  and reduces the observed number of recombinant
  offspring.
• Genes farther apart (for example, b-vg) are more
  likely to experience multiple crossing-over
  events.

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vg
cn
b
vg
b
cn
vg
cn
b
b
cn
vg
If you consider only the b and vg genes, the
gametes produced are all either b vg or b vg,
even though there has been crossing-over between
them. So you need to do a trihybrid cross to be
able to determine the true map distance between
genes. Corrected or true map distances can be
greater than 50!
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A recombinational map for few genes of
Drosophila chromosome 2.
Fig. 15.8
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Today, recombinational or genetic maps are
combined with physical maps to produce a complete
understanding of the relative location of
genes. Physical maps can be of several kinds.
Two very important ones are Cytogenetic
(chromosomal) maps using technologies like
FISH. Genomic maps from sequencing projects
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A comparison of a recombination map (distances
not shown, only relative gene order) and a
physical map (FISH), for chromosome 11 in people.
Dr. Julie R. Korenberg Neurogenetics,
UCLA. http//www.csmc.edu/csri/korenberg/images/pa
pers/figure2.jpg
page www.csmc.edu/csri/korenberg/chroma11.html
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A comparison of genetic and physical maps in
rice. The gene names are in red at the right,
with their genetic position (cM from the end of
the chromosome) in black next to them. The red
line is the physical map in kb. The total genome
size is 430 mb (million base pairs), so each
chrmosome is about 383 kb long.
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Lecture 9 Linkage
Readings Ch. 15, up to 15.3
Understand that Mendels laws have a physical
basis. locus, linkage, linked,
syntenic Understand that there can be many genes
on a single chromosome. linkage  Associate
Thomas Hunt Morgan with the fruit fly, Drosophila
melanogaster. wild-type phenotype mutant
phenotype natural mutations induced mutations.
 Understand that unlinked genes are recombined by
independent assortment understand that linked
genes may be recombined during crossing-over. par
ental types recombinants. Use recombination data
to map the location of genes on chromosomes.
linkage map, map distance
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Lecture 10 Sex Chromosomes Sex-Linked Genes  
Readings Ch. 15, 15.3 to end
Understand the significance of Morgans discovery
of the white-eyed male fly (review). sex
chromosomes. Understand that in many animals,
sex is determined chromosomally. X-Y system, X-0
system, Z-W system, haplodiploidy, SRY Understand
that many genes unrelated to sex are found on the
human X chromosome. X-linked traits.
 Identify the pattern of inheritance produced by
sex-linked recessive traits. hemizygous. Identify
some sex-linked genetic disorders in
humans. Duchenne muscular dystrophy, hemophilia.
Understand about X-inactivation. Barr
body. Identify another major class of chromosomal
disorders errors. nondisjunction, aneuploidy,
trisomy 21. Know what imprinting is.
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T. H. Morgan first showed, using a recessive
white eye mutant of the common fruit fly
Drosophila melanogaster, that a gene had to be
located on a specific chromosome.
Fig. 15.3
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Human X and Y chromosomes - these are homologous
over only a tiny portion of their length (at one
end). Most of the DNA is different between the
chromosomes. The X has many genes whose function
is not related to sex-determination, while the
few Y-linked genes are mostly involved with sex
determination.
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Sex-linked genes in humans

• Some genes on X-chromosome code for female
  traits some genes on Y chromosome code for male
  traits
• X chromosome has 164 million bases Y chromosome
  has 59 million bases
• Current estimate of X-linked genes range from
  729-748
• Current estimate of Y-linked genes is 78

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The X-Y system of sex determination we are
familiar with (humans, many other animals) is not
the only one...
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Fig. 15.10 - Basic pattern of inheritance of
X-Y-linked genes.Note that males are technically
hemizygous.
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Examples of X-linked genes for genetic disorders

• hemophilia
• red-green color blindness
• congenital night blindness
• high blood pressure
• Duchenne muscular dystrophy
• fragile X-syndrome

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Fig. 15.11
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Fig. 15.12
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Some terms for chromosomal disorders involving
different numbers of copies of chromosomes Euploid
y - polyploidy (tetraploid, etc.) means having
different numbers of whole genomes or sets of
chromosomes. Aneuploidy - means having too few or
too many of one chromosome. Trisomic means having
3 copies of one particular chromosome, rest of
karyotype normal diploid Monosomic means having 1
copy of one particular chromosome, rest of
karyotype normal diploid
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Fig. 15.15. Down syndrome.
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Two other chromosomal disorders in people
are Turner syndrome - monosomy X - only one X
chromosome, no Y - phenotype female, sterile,
generally otherwise normal Klinfelter syndrome -
disomy X, XXY, phenotype male, sterile,
developmental problems
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Fig. 15.7 Imprinting. Gene Igf2 is Insulin-like
growth factor-2, and the mutant produces a dwarf
mouse. But only the paternal allele is
expressed. (Expressed means to be transcribed
and translated).
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Lecture 10 Sex Chromosomes Sex-Linked Genes  
Readings Ch. 15, 15.3 to end
Understand the significance of Morgans discovery
of the white-eyed male fly (review). sex
chromosomes. Understand that in many animals,
sex is determined chromosomally. X-Y system, X-0
system, Z-W system, haplodiploidy, SRY Understand
that many genes unrelated to sex are found on the
human X chromosome. X-linked traits.
 Identify the pattern of inheritance produced by
sex-linked recessive traits. hemizygous. Identify
some sex-linked genetic disorders in
humans. Duchenne muscular dystrophy, hemophilia.
Understand about X-inactivation. Barr
body. Identify another major class of chromosomal
disorders errors. nondisjunction, aneuploidy,
trisomy 21. Know what imprinting is.