Transcript Sex chromosome

Chromosome Theory of Inheritance
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1902 Sutton and Boveri
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A chromosome is a linkage group of Mendelian
factors (GENES)
How many linkage groups in the human
species?
1920s Morgan et al.
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Genes are in a linear sequence on the
chromosomes, they can be mapped
Chromosomes in most animals
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pairs of autosomes
1 pair sex chromosomes
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XY heterogametic
XX homogametic
Human karyotype ->
Do more chromosomes mean more
intelligence?
Human
Chimpanzee
Dog
Cat
Alligator
Goldfish
Mosquito
Potato
Baker’s yeast
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I. Mammalian sex determination
= the Y system
A. Embryo is neither male
nor female
Week 7
How does embryo “know
to become male?
XY embryo sex chromosomes
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The Y determines sex…. XY = male XX =
female
B. SRY gene encodes TDF (Testes
determining factor, 1990)
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SRY (sex determining region Y)
Short arm (p)
TDF is a 20 aa protein (a
transcription factor)
TDF stimulates the growth of
testes -->
testosterone ---> sperm ducts,
male brain “sensitization”
XX males: If SRY crosses over to the X
chromosome during meiosis (formation of sperm)
Father during meiosis
X from father +
X from mother
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A 17 year old female presented with “streak”
ovaries, no uterus, no menstrual cycle
XY female
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Embryo has Y chromosome but does not
develop as male
Mutation in SRY  ?
II. Other sex determination systems
A. Drosophila
Ratio of X to sets of autosomes
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embryo “calculates” ratio
X/A = 1 or >1 ------> female
X/A = 0.5 or <0.5 --------> male
X/A between 0.5 and 1 ---> intersex
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What is the sex of an XY fly with 2 sets of autosomes?
What is the sex of a fly with with 2 sets of autosomes
but 1 X chromosome
What is the sex of a triploid fly with 2 X chromosomes?
B. ZW system - birds
Females are ZW
(heterogametic)
 Males are ZZ
(homogametic)
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PCR analysis of sex chromosomes
C.Temperature sex determination (TSD)
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In some reptiles sex is not
determined genetically!
(Varies widely)
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majority of endangered reptiles
use TSD - sea turtles, Galapagos
tortoises, alligators, crocodiles
Parthenogenesis – eggs
develop without sperm
(asexual)
Komodo dragon
Parthenogenesis
ZW system, all offspring
of parthenogenesis are male
Why?
IV. Dosage Compensation
(mammals)
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Females have 2 Xs, males have 1 X. Do
females have an extra dose of X-linked
genes/alleles?
X chromosome inactivation Lyon, 1961
Observe dense “Barr body” at edge of nucleus
in female cells
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Heterochromatic (stains darker)
Male cell
female cell
cell with 2 Barr bodies
Number of X chromosomes?
Random X-inactivation, mechanism
~1000 cell embryo
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random inactivation of X
XIC
X
X
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XIC, Xist gene on X chromosome
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transcribed 24 hours prior to inactivation
mRNA “cages” X-chromosome
caged X becomes a Barr body
Which X is inactivated appears to be
random
Barr body
mRNA
Embryo develops patches
Female mosaics
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All females heterozygous for X-linked traits
are mosaics for those traits.
red/green colorblindness
XCXc
phenotype = ?
Look at retina of heterozygous female
Anhydrotic ectodermal dysplasia
XAXa females
XaY males
Tooth + nail
abnormalities, life
threatening hyperthermia,
sparse hair
Similarities and differences X and Y
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Most genes on Y are for
development and fertility
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(Human has ~80 Y genes)
(Kangaroo has only SRY on the Y)
~ 80 genes
Pseudoautosomal region of
the X and Y
•~12 genes on X and Y
•regions allow X and Y to
pair during meiosis
•pseudoautosomal genes are
also transcribed from the
inactivated X!
•both males and females have
2 active copies of these genes
Chromosomal Abnormalities
KARYOTYPE
1. Obtain white blood cells from or fetal cells from
amniotic fluid
2. Proliferation via growth factor add colchicine at
metaphase to arrest spindle formation
3. add water to swell cell -> squash
4. stain ->photograph
Detects number of chromosomes,
sex, chromosomal abnormalities
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Amniocentesis usually done week 14
Karyotype and analyze
fluid for enzyme
defects
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Chorionic villus sample (CVS) usually
done week 8
More risk, but
earlier results
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Arrange in pairs according to:
 decreasing size
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centromere position
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banding pattern
METACENTRIC
SUBMETACENTRIC
ACROCENTRIC
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metacentric (1) submetacentric (9)
p arm is the upper, shorter arm
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Normal
male
46, XY
Which are
meta-,
submetaacrocentric?
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Aneuploidy (versus euploidy)
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Trisomy (not triploid)
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47, 21+
(1/800 live births)
21 may be small, but contains 33,546,361 bp of DNA!
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Down Syndrome (J. Langdon H. Down, 1866)
effects
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Developmental delays
Possible heart defects,
hearing loss, hypotonia,
thyroid problems, obesity
Epicanthic eye folds
Wide tongues
Greater risk of
Alzheimer’s
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Trisomy 13 (Patau)
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Fatal< 1 year (usually)
Deaf, blind, clyclopia, polydactly,
cleft palate
1/5000 live births
47, XY, 13+
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47, XY, 18+ (Edward’s)
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< few months
1/5000 live
births
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Human trisomies of the sex
chromosomes (see pg 293)
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47, XXY = Klinefelter’s
47, XXX
47, XYY
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Monosomy (only 1 viable in humans!)
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45 X,
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Turner Syndrome (1/2000 live births)
Partial monosomy 46, 5p
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Cri du Chat
Arises due to a deletion on the short arm of
chromosome 5
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Cri du Chat 46, 5p-
1/50,000 live
births
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pseudodominance for
deleted region
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Microcephaly, myotonia,
“cry of cat”, retardation
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if individuals make it
past childhood,
symptoms lessen
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Polyploidy = extra SETS of
chromosomes
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# in humans
Triploid, tetraploid
Octoploid etc..
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Many plants are
polyploid
Some bees and wasps
are monoploid
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In humans
Monosomy
Trisomy
Tetrasomy
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Deletions (del)
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can observe large ones by karyotype
If centromere is lost, then chromosome will be lost
Heat, chemicals, radiation
Unequal crossing over during meiosis
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46,XX,del(7)(q21.12,q21.2)
Pseudodominance
 Lethal if both chromosomes
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Leads to problems during meiosis
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Duplications
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segment of a chromosome doubles
May be tandem or reverse
problems during meiosis
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dup(5)(qter->q33.1::p15.3->qter)
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Sample of cord blood from
stillborn male with anencephaly
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Inversions (inv)
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180o turnaround of segment
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no loss of genetic material
may change length ratio of p/q arms
Position effect
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change in gene position with respect to
centromere
being near heterochromatic region may
influence expression
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Translocations - segment moves to other
chromosome - interstitial or reciprocal exchange
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t (13;14)
Individual has all
genetic material, but
what about gametes?
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t(11;13) (q21;q14.3)
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the parent who has the
translocation is
phenotypically normal
as all genetic info is
present
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The gametes, however,
are not as evidence by
multiple miscarriages
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Translocation (cont.)
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Robertsonian fusion
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ends of 2 acro- or telocentric break/fuse
45 chromosomes but no, or little, loss of genetic
material
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