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Sex inheritance
• In humans, fruit flies, XX = female; XY = male.
• Inheritance of sex is just like any other trait,
except it involve inheritance of an entire
chromosome.
Because there are
genes on sex
chromosomes,
inheritance of certain
traits can be sex-linked.
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Sex Linkage and Determination
• Early 1900s, Thomas Hunt Morgan was doing
classical genetics on fruit flies, looking for
mutants and checking out the patterns of
inheritance.
• He studied the white eye phenotype and
discovered something odd…
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What Morgan saw
Reciprocal cross
produced a
different result:
Inheritance of
eye color
depended on
sex of the fly.
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Morgan and the F2 generation
When the all red eyed F1
heterozygotes were crossed,
close to a 3:1 ratio was
observed, but the traits were not
evenly divided between the
sexes.
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Explanation
• The traits of sex and eye color did not assort
independently (as the traits in peas did).
• The traits are linked.
• The gene is NOT PRESENT on the Y
chromosome.
R = red eye
R = white eye
XX = female
XY = male
significance
• With regard to X linked traits, males have only
one allele, not two. They are said to be
hemizygous.
• Morgan’s work led to the understanding that
genes are located on chromosome’s because
inheritance of certain traits corresponded to
inheritance of a visibly different chromosome.
• Inheritance of X-linked traits results in typical
crisscross inheritance: mother to son.
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Crisscross inheritance
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Carrier mother passes allele to son who expresses it,
passes allele to daughter who carries it, etc.
Hemophilia & color blindness: examples in humans.
http://www.udl.es/usuaris/e4650869/docencia/segoncicle/genclin98/temes_teoria/imatge
s_temes_teoria/image3.gif
Sex determination
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• Different organisms have different
chromosomal mechanisms for determining sex.
– XX/XO: typically, the male has one copy.
• Nematodes, e.g. C. elegans
– XX/XY: as in humans, fruit flies, XX = female; XY =
male.
• Heterogametic sex is the one that produces a
mixture of gametes. Usually the male but:
– Female can be heterogametic in some species
– Designation is ZZ/ZW where female is ZW
More on sex determination
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• Temperature affects sex determination in many
reptile species
– Females result from low, high, or extremes of
temperature.
– Hypothesis:
History
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• Sex determination studies began in late 1800’s
• Work in humans started around 1912, but didn’t
get it right until 1956.
• Keys to understanding sex determination in
humans:
– Improved karyotype methods
– Study of aneuploidy of sex chromosomes
– Aneuploidy is the wrong number of a particular
chromosome.
– Aneuploidy results from non-disjunction
Abnormalities in chromosome number result
from non-disjunction
Homologues fail to separate during Meiosis I.
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Abnormalities in chromosome number result
from non-disjunction-2
Sister chromatids fail to separate during Meiosis II.
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Evidence for XX/XY
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• 47, XXY Klinefelter syndrome
– male in appearance, but some feminization; sterile.
– slow to learn, but not retarded.
– XXXY etc. similar, but more severe symptoms
• 45, XO Turner syndrome
– Monosomy, the only one occurring in humans
– female, sterile, short webbed neck, broad chest,
short.
– majority aren’t born
• If XXY is still male and XO is female
– Y must be determinant of maleness
About the Y
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• Y chromosome has been shrinking.
– Now missing many of genes that X has.
• Two regions: PAR and MSY
• PAR= pseudoautosomal region
– Regions near p telomere and q telomere are
homologous to X chromosome. Crossing over can
occur there during meiosis. Because of this, genes
in this location do not behave as sex-linked traits,
thus said to be pseudoautosomal because they
behave like genes on autosomes rather than sex
chromosomes.
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Structure of Y
universe-review.ca/R11-14-Ychromosome.htm
http://www.asiaandro.com/
1008-682X/4/259fig.jpg
Human Genome
project has
revealed much
about the Y
chromosome.
Male specific region Y (MSY)
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• X-transposed region
– 99% identical to X chromosome region, but only 2
genes; the rest are not expressed.
• X-degenerative region
– Contains DNA related to X chromosome regions
– Several functional genes and pseudogenes
– Contains SRY that codes for testis-determining
factor, necessary for maleness during development.
• Ampliconic region
– Highly similar or repeated genes, some related to
male development and fertility.
Evidence for SRY
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• SRY contains gene for testis determining factor
• Crossing over in meiosis
– Males with two X chromosomes; SRY found on one
– Females with X and Y; SRY is missing from Y
• Transgenic mice
– Remove SRY from Y chromosome
– Mice are XY but are female
– Reciprocal experiment also done
Article about Y chromosome
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• http://images.google.com/imgres?imgurl=http://www.tx
twriter.com/onscience/OSpictures/Y%2520chromosom
e%2520repair.jpg&imgrefurl=http://www.txtwriter.com/
onscience/Articles/ychromosome.html&h=927&w=504
&sz=160&hl=en&start=14&tbnid=hTINd2RIkH59cM:&t
bnh=147&tbnw=80&prev=/images%3Fq%3DY%2Bchr
omosome%26svnum%3D10%26hl%3Den%26rls%3D
GGLG,GGLG:2005-29,GGLG:en
• Copy and paste
Gene dosage
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• It matters how many copies of genes there are.
– Snapdragons: heterozygous flowers are pink.
– Multiple histone genes.
– Too many of some genes is deleterious.
• 3 copies of chromosome 21 = Down Syndrome
• What about sex chromosomes? XX vs. XY
– Y chromosomes are missing most of genes X has.
– So, if 1 set of genes on the X is good for males, is
two sets (2 X chromosomes) bad for females?
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Dosage compensation: Barr, Ohno, and Lyon
• Barr noticed that in the nucleus of females, but not
males, a darkly staining body is visible.
• Ohno hypothesized that this was an inactivated X
chromosome in females so that there would only be 1
functional copy of genes, as in males.
• Inactivated X is called a Barr body.
• Individuals with incorrect numbers of sex
chromosomes have appropriate number of Barr
bodies.
– E.g. XXX females have 2 Barr bodies
Lyon Hypothesis
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• X chromosome inactivation takes place early in
development.
• In placental mammals, it can be either X chromosome.
– All the descendents of that cell have the same X
chromosome inactivated.
– Results in a mosaic, patches of tissue with different
lineages. Seen with X-linked traits.
• Human females: anhidrotic epidermal dysplasia,
no sweat glands; female has patches of skin w/o
sweat glands, cells descended from a cell in
which the X chromosome with the normal gene
was inactivated.
• G6PD alleles; Patches of color blindness
Descent of cells:
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How mosaics are made.
Events during
development.
Two homologous
chromosomes, blue & red.
Black indicates
inactivation = Barr
body
Formation of Barr bodies-2
Classic example: the calico cat.
One X chromosome codes for
orange fur, the other for black. Cat
shows characteristic mosaic patterns
caused by one or the other X
chromosome being inactivated.
White fur results from the effect of
another gene.
http://www.petstreetmall.com/merchant/Embroidery/Cat/CalicoCatBody.gif.jpe
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Molecular basis of Barr body formation
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• Xic is a region on the X near the centromere.
• Xic region includes a region called Xist (X inactivation
specific transcript)
– This area is transcribed, but RNA isn’t used to make
a protein; it binds to the DNA of the rest of the X
chromosome.
– This promotes molecular changes that inactivate
the chromosome including extensive methylation
(except for XIC) and condensation of DNA (into
smaller space).
• In the OTHER X chromosome, Xic region is
methylated so it will NOT be active.
Active and inactive regions
Red: active genes.
Black: inactive
Xic is responsible for this
process; if moved to an
autosome, that chromosome
will be inactivated.
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