1 Sex Linkage and Determination In humans, fruit flies, XX = female; XY = male. Because there are...
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Transcript of 1 Sex Linkage and Determination In humans, fruit flies, XX = female; XY = male. Because there are...
1Sex Linkage and Determination
• In humans, fruit flies, XX = female; XY = male.• Because there are genes on sex chromosomes,
inheritance of certain traits can be sex-linked.• 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…
2What Morgan saw
Reciprocal cross produced a different result:
Inheritance of eye color depended on sex of the fly.
3Morgan and the F2 generation
When the all red eyed F1 heterozygotes were crossed, a 3:1 ratio was observed, but not evenly divided between the sexes.
4significance
• 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.
5Crisscross inheritance
http://www.udl.es/usuaris/e4650869/docencia/segoncicle/genclin98/temes_teoria/imatges_temes_teoria/image3.gif
Carrier mother passes allele to son who expresses it, passes allele to daughter who carries it, etc.
Hemophilia & color blindness: examples in humans.
6Sex determination
• 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
7More on sex determination
• Temperature affects sex determination in many reptile species– Females result from low, high, or extremes of
temperature.– Hypothesis:
8History
• 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
9Abnormalities in chromosome number result from non-disjunction
Homologues fail to separate during Meiosis I.
10Abnormalities in chromosome number result from non-disjunction-2
Sister chromatids fail to separate during Meiosis II.
11Evidence for XX/XY
• 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
12Other sex chromosome aneuploidies
• 47, XXX– Some phenotypically normal
– Others, sterility, mental retardation
• 47, XYY– 1965 study: higher number of inmates with XYY– revisited: no real correlation with criminal behavior
• Controversial research, no clear answer.– taller than average, slightly lower IQ on average.
13About the Y
• 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.
14Male specific region Y
• 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– Contains SRY that codes for testis-determining
factor, necessary for maleness during development.
• Ampliconic region– Highly similar genes related to male development
and fertility.
15Evidence for SRY
• 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
16Gene dosage
• 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?
17Dosage 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
18Lyon Hypothesis• 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.• Human females: anhidrotic epidermal dysplasia, no
sweat glands; X linked gene, 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
19
Descent of cells:
How mosaics are made.
Two homologous chromosomes, blue & red.
Black indicates inactivation = Barr body
20Formation of Barr bodies-2
http://www.petstreetmall.com/merchant/Embroidery/Cat/CalicoCatBody.gif.jpe
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.
21Molecular basis of Barr body formation
• 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.
22Active and inactive regions
Red: active genes.
Black: inactive
23Human sexuality
• http://info.med.yale.edu/therarad/summers/wgss255a%20lecture%2013.ppt#1
• Interesting powerpoints with more questions than answers– Caution: graphic images