cytogenetics and sex determination Flashcards
3 types of chromosome variation
metacentric - middle
acrocentric - close to end
telocentric - at end
Cytogenetics
the study of inheritance by visualising the structure
and function of chromosomes
what determines sex
genes (not just those on sex chromosomes) rather than chromosomes are the
basis of sex determination.
Genetic sex determining systems
normally have populations of ½ females and ½
males.
- one sex is heterogametic, the other is homogametic.
Non-genetic systems
can have unequal numbers of the two sexes.
Sex chromosomes in different animal species
X-0 system in certain insects - X = male, XX = female Z-W system in birds - ZZ = male, ZW = female haplo-diploid system in bees 16 haploid = male, 32 diploid = female
Why isn’t the ratio of males to females 1:1
- Do males produce more Y-bearing than X-bearing sperm?
- Are Y-bearing sperm more viable and motile?
- Is the egg surface more receptive to Y-bearing sperm?
temperature-dependant sex determination
female to male as temp increases
male to female as temp increases
female are at extreme low and high temp, male at middle
do x and y form a homologous pair
yes in meiosis
but only in the PAR regions 1 and 2
where is SRY located and what does it do
PAR1
encodes the protein (testis-determining factor
or TDF
How was the SRY discovered?
Crossing-over occurs within PAR
• Typically within PAR1 (because it’s larger)
• Discovered in abnormal cases where
karyotype didn’t match sex phenotype
- cross-over below SRY, making them 46,XY, female that are sterile
Is the same system used in Drosophila?
Sex determined by ratio of X chromosomes to autosomes • 1 X : 3 pairs autosomes = male • 2 X : 3 pairs autosomes = female 2 or more x = female 1x =male e.g. X = sterile male XXY = female
Dosage compensation
There is compensation for the different gene dosages between males
and females – called Lyonisation
maternal and paternal X-inactivation
In females (at about 2 weeks ~ 500 cells) a random X chromosome is inactived in EACH somatic cell • The inactivation state is maintained in all progeny from that cell • Tissues composed of ~50% maternally inactivated & 50% paternally inactivated
Barr bodies
Inactivated X chromosomes called Barr bodies
• But silenced X chromosome is reactivated at oogenesis
number of barr bodies
Number of Barr bodies per nucleus = number of X chromosomes – 1 • XX = 1 Barr body • XXX = 2 Barr bodies • XXY = 1 Barr body
Example: Tortoiseshell cats (& Calico cats)
X-linked orange gene, two alleles: X o+ - black coat colour (dominant) X o - orange coat colour So, tortoiseshell cats are always heterozygotes for the pigment genes. They are moisaics, with some cells expressing orange allele and other expressing black allele
Human example: Red-green colour blindness
X-linked recessive trait
• In males
• If recessive (mutant) allele inherited = individual colourblind
• If dominant (WT) allele inherited = individual have normal colour perception
• In females
• If homozygous dominant for wildtype allele = normal colour perception
• If homozygous recessive for mutant allele = individual colourblind
• If heterozygous = retinas are mosaics (colour perception usually good enough)
X-inactivation
- Active X chromosome is euchromatic
- Silenced X chromosome is mostly heterochromatic
- Most genes are not expressed
- However some regions escape silencing on inactive X chromosome
- These regions are the PAR and the X Inactivation Centre (XIC)
- Within XIC encodes a lncRNA (Xist)
- X - Inactive specific transcript
Mechanism of X-inactivation
- initiation
- spreading
- maintenance
initiation
Xist gene is ONLY expressed on the
silenced X chromosome (or
chromosomes if XXX , etc)
Xist is a long non-coding RNA
spreading
Xist RNA spreads out along the silenced X chromosome(s) and coats them Xist coating attracts histone modifying enzymes inactivating the chromosome Note: Xist and PAR escape silencing
maintenance
Xist expression is maintained on silenced
X chromosome
X-inactivation can be reversed (for
instance meiosis)
