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Chromosome Theory of Inheritance. 1902 Sutton and Boveri A chromosome is a linkage group of Mendelian factors (GENES) How many linkage groups in the human species? 1920s Morgan et al. Genes are in a linear sequence on the chromosomes, they can be mapped. Chromosomes in most animals. - PowerPoint PPT Presentation
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Chromosome Theory of Inheritance 1902 Sutton and Boveri
A chromosome is a linkage group of Mendelian factors (GENES)
How many linkage groups in the human species?
1920s Morgan et al. Genes are in a linear sequence on the
chromosomes, they can be mapped
Chromosomes in most animals pairs of autosomes 1 pair sex chromosomes
XY heterogametic XX homogametic
Human karyotype ->
Do more chromosomes mean more intelligence?
Human 46Chimpanzee 48Dog 78Cat 72Alligator 32Goldfish 94Mosquito 6Potato 48Baker’s yeast 34
I. Mammalian sex determination = the Y system
A. Embryo is neither male nor female
Week 7 How does embryo “knowto become male?
XY embryo sex chromosomes The Y determines sex…. XY = male XX =
female
B. SRY gene encodes TDF (Testes determining factor, 1990)
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
A 17 year old female presented with “streak” ovaries, no uterus, no menstrual cycle
XY female 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 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
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)
PCR analysis of sex chromosomes
C.Temperature sex determination (TSD) In some reptiles sex is not
determined genetically! (Varies widely)
majority of endangered reptiles use TSD - sea turtles, Galapagos tortoises, alligators, crocodiles
Parthenogenesis – eggs
develop without sperm
(asexual)Komodo dragonParthenogenesisZW system, all offspringof parthenogenesis are maleWhy?
IV. Dosage Compensation (mammals) 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 Heterochromatic (stains darker)
Male cell female cell cell with 2 Barr bodies
Number of X chromosomes?
Random X-inactivation, mechanism
~1000 cell embryo random inactivation of X
XIC, Xist gene on X chromosome transcribed 24 hours prior to inactivation mRNA “cages” X-chromosome caged X becomes a Barr body
XICX
X
Which X is inactivated appears to be random
mRNA
Embryo develops patches
Barr body
Female mosaics 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 dysplasiaXAXa females XaY malesTooth + nail
abnormalities, life
threatening hyperthermia,
sparse hair
Similarities and differences X and Y Most genes on Y are for
development and fertility (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
23
Chromosomal AbnormalitiesKARYOTYPE
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
24
Amniocentesis usually done week 14
Karyotype and analyze fluid for enzymedefects
25
Chorionic villus sample (CVS) usually done week 8
More risk, butearlier results
26
Arrange in pairs according to: decreasing size
centromere position
banding pattern
ACROCENTRIC
METACENTRIC
SUBMETACENTRIC
27
metacentric (1) submetacentric (9)
p arm is the upper, shorter arm
28
Normalmale
46, XY
Which are meta-, submeta-acrocentric?
29
Aneuploidy (versus euploidy) Trisomy (not triploid)
47, 21+
(1/800 live births)
21 may be small, but contains 33,546,361 bp of DNA!
30
Down Syndrome (J. Langdon H. Down, 1866)
effects Developmental delays Possible heart defects,
hearing loss, hypotonia, thyroid problems, obesity
Epicanthic eye folds Wide tongues Greater risk of
Alzheimer’s
31
Trisomy 13 (Patau) Fatal< 1 year (usually) Deaf, blind, clyclopia, polydactly,
cleft palate 1/5000 live births
47, XY, 13+
32
47, XY, 18+ (Edward’s) < few months
1/5000 live births
33
Human trisomies of the sex chromosomes (see pg 293) 47, XXY = Klinefelter’s 47, XXX 47, XYY
34
Monosomy (only 1 viable in humans!) 45 X,
Turner Syndrome (1/2000 live births)
Partial monosomy 46, 5p- Cri du Chat Arises due to a deletion on the short arm of
chromosome 5
35
Cri du Chat 46, 5p- 1/50,000 live births
pseudodominance for deleted region
Microcephaly, myotonia, “cry of cat”, retardation
if individuals make it past childhood, symptoms lessen
36
Polyploidy = extra SETS of chromosomes # in humans Triploid, tetraploid Octoploid etc..
37
Many plants are polyploid
Some bees and wasps are monoploid
38
In humans
Monosomy
Trisomy
Tetrasomy
39
can observe large ones by karyotype If centromere is lost, then chromosome will be lost Heat, chemicals, radiation Unequal crossing over during meiosis
Deletions (del)
40
46,XX,del(7)(q21.12,q21.2)
Leads to problems during meiosis
Pseudodominance Lethal if both chromosomes
41
Duplications segment of a chromosome doubles May be tandem or reverse problems during meiosis
42
dup(5)(qter->q33.1::p15.3->qter) Sample of cord blood from
stillborn male with anencephaly
43
Inversions (inv) 180o turnaround of segment
no loss of genetic material may change length ratio of p/q arms
Position effect change in gene position with respect to
centromere being near heterochromatic region may
influence expression
44
Translocations - segment moves to other chromosome - interstitial or reciprocal exchange
t (13;14) Individual has all
genetic material, but what about gametes?
45
t(11;13) (q21;q14.3)
the parent who has the translocation is phenotypically normal as all genetic info is present
The gametes, however, are not as evidence by multiple miscarriages
46
Translocation (cont.) Robertsonian fusion
ends of 2 acro- or telocentric break/fuse 45 chromosomes but no, or little, loss of genetic
material