BMS2042 Lecture Notes - Lecture 10: Mitosis, Xyy Syndrome, Penetrance
30 May 2018
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Week 4. Cytogenetics, sex determination, sex
chromosomes, aneuploidy and Changes in
chromosome structure
CYTOGENETICS, SEX DETERMINATION, SEX CHROMOSOMES AND ANEUPLOIDY
• Cytogenetics: examination/visualisation of chromosomes
• Humans have 46, 23 pairs of homologues
22 pairs of autosomes
1 pair of sex chromosomes
• Chromosomes vary in size and centromere position:
o Metacentric: in middle
o Acrocentric: towards end
o Telocentric: at end
• G banding:
o Giemsa stain – particular pattern for each chromosome
o Pre-treat chromosomes with agent that loosens DNA protein interactions then stain with
Giemsa -> G bands
• Nomenclature of human karyotypes and chromosomes:
• Chromosome painting:
o Most recent method of distinguishing between chromosomes:
FISH (fluorescent in situ hybridisation) procedure
1. Denature dsDNA
find more resources at oneclass.com
find more resources at oneclass.com
2. Make a probe that contains many sequences from an individual chromosome
3. Label probe with fluorescent dye
4. Hybridise probe to chromosome spreads in situ (in tissue/organism)
Only one chromosome type fluoresces -> has been painted
o Five different dyes developed
o Various combinations of these dyes are used to label probes
-> each combination gives a different colour
o Works well for large scale eg. cancer where you get large scale chromosome
rearrangement
• Most diploid organisms have only sexual reproduction
• Genetic sex determining systems: normally have populations of ½ females and ½ males
-have gene that is different
-one sex is heterogametic, other is homogametic
• Non-genetic systems: can have unequal numbers of the two sexes
-environment determines whether male or female eg. crocodiles
->due to temp sensitive enzyme aromatase (androgen -> estrogen), not well understood
• Primary sex ratio
o at conception
o hard to measure
• Secondary sex ratio
o At birth
o Easy to measure
o ~1.06-1.15
o More males born than females
o Do males produce more Y bearing sperm than X
-are they more viable and motile because they carry less DNA?
-is the egg more receptive to Y?
find more resources at oneclass.com
find more resources at oneclass.com
• Sex determination in mammals
o Presence of Y determines maleness
o Predicted 1098 genes in X chromosome
o Predicted 78 genes in Y chromosome (mostly for sperm production)
o Pseudo-autosomal: genes in these regions are shared by X and Y
-> at the end of chromosomes (homologous) -> allows planning during meiosis
-always one crossover at the end of the short arm (p)
o Sex determining region (SRY)
Close to pseudo-autosomal region
Located through rare abnormal cases of XX males and XY females
-> arise by rare crossovers below SRY gene
-> individuals sterile, defect is not transmitted
In drosophila: 2 or more X = female, 1 X = male, Y is only required for functional
sperm
• Dosage compensation and X inactivation:
o Ma gees o X are’t ioled i se differees
o Compensation for differences in gene dosage between males and females occur
(because females have double)
-> can observe that both sexes have same amount of enzyme despite females having
double gene
o This corrects the imbalance
o Achieved by random inactivation of one of the two X chromosomes in each cell early in
development
o Inactivated state is propagated to all progeny cells – lyon hypothesis
o Most gees o iatiate X are sileed ~5% are’t
o Silenced X is reactivated in oogenesis
o Inactivated chromosome = barr body -> darkly stained, highly condensed structure
(heterochromatin)
Barr bodies = number of X present - 1
• Expression of X-linked genes:
o Due to X inactivation, female mammals are natural mosaics for X genes
eg. tortoiseshell cats are always heterozygous females due to x-linked orange gene
-> some express Xo+ some express Xo (both are partially inactivated)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Cytogenetics, sex determination, sex chromosomes, aneuploidy and changes in chromosome structure. Cytogenetics, sex determination, sex chromosomes and aneuploidy: cytogenetics: examination/visualisation of chromosomes, humans have 46, 23 pairs of homologues. Giemsa -> g bands: nomenclature of human karyotypes and chromosomes, chromosome painting, most recent method of distinguishing between chromosomes: Make a probe that contains many sequences from an individual chromosome. Hybridise probe to chromosome spreads in situ (in tissue/organism) Only one chromosome type fluoresces -> has been painted: five different dyes developed, various combinations of these dyes are used to label probes. One sex is heterogametic, other is homogametic: non-genetic systems: can have unequal numbers of the two sexes. Environment determines whether male or female eg. crocodiles. > at the end of chromosomes (homologous) -> allows planning during meiosis. Always one crossover at the end of the short arm (p: sex determining region (sry) Located through rare abnormal cases of xx males and xy females.
