Sex chromosomes and sex determination

Question 1

Cytogenic

Answer 1

Cytogenetics – is the study of inheritance by visualising the structure
and function of chromosomes
Humans have 46 chromosomes (23 homologous pairs)
44 autosomes (22 pairs)
2 sex chromosomes (1 pair – XY or XX)

Question 2

Chromosome structure

Answer 2

• Sister chromatids joined to each
other at centromere
• Genetic material the same between sister
chromatids
• Chromosomes classified based on
centromere position
• P = short arm (think “Petite”)
• Q = long arm

Metacentric = middle 
submetacentric= between middle and end 
telocentric = the end 
acrocentric = close to the end

Question 3

• Staining methods – G-banding

Answer 3

• During metaphase chromosome condense
(making them visible)
• This is driven by chromatin compaction
• Light and dark bands on the chromosomes
are revealed following Giemsa staining

Question 4

•G-banding nomenclature

Answer 4

Bands are numbered starting from centromere
working outward
• So 1 is closer to centromere than 2
• Main bands can be divided into smaller bands
• Smaller numbers are always closer to the centromere

e.g. 3p22.1

Question 5

Sex determination mode

Answer 5

Wide range of reproductive modes found:
- Some organisms entirely asexual
- Some alternate between short periods of sexual reproduction and long periods of
asexual reproduction.
- Most diploid organisms have only sexual reproduction

Question 6

Sex determination requires

Answer 6

Requires sexual differentiation or phenotypic dimorphism of the two sexes.
Heteromorphic chromosomes (sex chromosomes) distinguish the two sexes.
But, genes (not just those on sex chromosomes) rather than chromosomes are the basis of sex determination.

Question 7

Basis of sex determination can be genetic or nongenetic what is the difference

Answer 7

Genetic sex determining systems normally have populations of ½ females and ½
males.
- one sex is heterogametic, the other is homogametic (same sex chromosome morphology).
Non-genetic systems can have unequal numbers of the two sexes

Question 8

Sex chromosome in insects

Answer 8

Many insects
Males have a single X (still called heterogametic)
Females have two X chromosomes
Males produce gametes containing EITHER X or no
sex chromosome (XO)
 still heterogametic
Still diploid for all autosomes

Question 9

Bird and some reptiles

Answer 9

Males are homogametic (ZZ)

Females are heterogametic (ZW)

Question 10

Honeybees

Answer 10

Males are haploid

Females are diploid

Question 11

Why isn’t the ratio of males to females 1:1

Answer 11

Secondary sex ratio (ratio at birth) – more males than females:
- Varies in different countries from ~1.06 to 1.15
Sex ratio at conception (primary sex ratio) difficult to measure / data unreliable
Why is it not 1.0?
- 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?

Question 12

Temperature-dependent sex determination happen in

Answer 12

some reptiles

Question 13

How Sex determination in mammals was identified

Answer 13

Investigation of abnormal karyotypes led to identification of human sex determination system
Found that:
Female - X / XX / XXX
Male – XY / XYY / XXY

Question 14

Y chromosome determines

Answer 14

male sex in humans
• In males X & Y chromosomes form a homologous pair (for meiosis)
• But only homologous in pseudoautosomal regions 1 / 2 (towards the end of the chromosmome)
• X chromosome encodes numerous genes, involved in numerous bodily processes
• Y chromosome encodes few genes – mainly associated with sperm production

Question 15

Where in the Y confers male sex?

Answer 15

• Sex-determining Region on the Y – (SRY)
• Located close to PAR1
• Encodes a protein (testis-determining factor
or TDF)
• At ~6-8 weeks TDF causes undifferentiated
gonadal tissue to develop into testes

Question 16

How was the SRY discovered?

Answer 16

• 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 (X chromosome containing the SRY gene = male )
• 46 XX – males (X chromosome containing the SRY gene and PAR1)
• 46 XY – females( Y chromosome containing the PAR from the X chromosome no SRY)
• But these individuals are sterile, so cannot
be transmitted

Question 17

What happens if SRY is inserted into a normal XX female zygotes of mouse

Answer 17

• Transgenic mouse developed male sex

characteristics (remained XX

Question 18

Is the same system used in Drosophila?

Answer 18

• Drosophila also have X and Y chromosomes
• Typically XX = female; XY = male
• Sex determined by ratio of X chromosomes to autosomes
• 1 X : 3 pairs autosomes = male
• 2 X : 3 pairs autosomes = female

Complex series of transcription factors determined by ratio of X chromosomes to autosomes

Question 19

Dosage compensation

Answer 19

Dosage compensation refers to the equalization of most X-linked gene products between males, which have one X chromosome and a single dose of X-linked genes
• Many genes on the X chromosome perform other functions not related to sex characteristics
• There is compensation for the different gene dosages between males and females – called Lyonisation-AKA X-inactivation

Question 20

How Dosage compensation is achived>

Answer 20

• Remember epigenetic marks are mostly deleted at fertilisation
• 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

Question 21

Barr bodies

Answer 21

• Inactivated X chromosomes called Barr bodies

* But silenced X chromosome is reactivated at oogenesis

Question 22

Number of Barr bodies

Answer 22

• Number of Barr bodies per nucleus = number of X chromosomes – 1
• XX = 1 Barr body
• XXX = 2 Barr bodies
• XXY = 1 Barr body

Question 23

Human example: Red-green colour blindness - mosaicism

Answer 23

• 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)

Question 24

X-inactivation

what regions escape the silencing on inactive X chromosome

Answer 24

• 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

Question 25

Mechanism of X-inactivation

Answer 25

1. Initiation
Xist gene is ONLY expressed on the silenced X chromosome (or chromosomes if XXX , etc)
Xist is a long non-coding RNA
Xist does not encode a protein & is not translated
Xist is not transcribed on active (non-silent) X
chromosome
2. 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
3. Maintenance
Xist expression is maintained on silenced
X chromosome
X-inactivation can be reversed (for
instance meiosis)