February 14th CLASS - Happy valentines day!

- We have an automatic extension of three days (March first) for the project due on
the 26th
Sexual Dimorphism
● Sexual Dimorphism - Morphological differences between the sexes
○ Examples: mandarin ducks, orangutan males are larger than females. Same
species but with differences between the sexes.
○ Determined by pair of sex chromosomes
○ XX = female
○ XY = male
○ Differ from autosomes, which do not determine sex

Human Sex Chromosomes

● Pseudo-autosomal regions (PAR) 1 and 2: short, autosomal-like homologous regions
○ Approximately 30 genes
○ One (XY) or both (XX) regions pairs and cross-over during meiosis
● Differential regions of X and Y chromosomes contain genes that are unique to these
chromosomes
○ These are sex-linked genes and show ex-linked patterns of inheritance
■ E.g. SRY gene on the Y chromosome
 - Sex is determined by the presence of hte gene SRY, present on the Y -chromosome
(sex determining gene
- SRY is not found on the X chromosome
- Which is why people with 2 X chromosomes display female characteristics
- Both the X and Y chromosomes have the “pseudoautosomal regions/PAR regions)
- These regionscontain 30 genes and behave as autosomes on the X and Y
chromosomes
- Everything else between those two poles are differential regions of the X and Y
chromosomes (regions between PAR = unique to the X/Y)
- PAR regions are able to participate in crossing over events during meiosis
- This is the exchange of genetic information during the production of the gametes
- PAR regions = homologus, experience crossing over
- Pseudoautosomal region are always expressed - do not experience
X-inactivation
Inheritance of sex chromosomes
● XX individuals inherit an X-chromosome from each parent
● XY individuals inherit their X chromosome only from their mothers and Y chromosome
from their fathers
● Have an XX child = 50% and XY child = 50%

Y–linked patterns of inheritance

● The trait is seen only in males
● All male descendants of an affected man will exhibit the trait
● Females never inherit the trait and thus cannot pass it on to her offspring
● E.g. SRY gene
● X-linked patterns of inheritance is more complicated
○ Males have ONE X and ONE Y = dosage is one per chromosome
○ Females have 2 X chromosomes BUT the dosage is not double
X-chromosome inactivation
● Biological female individuals have twice as many X chromosomes as biological males
● X dosage compensation: one X chromosome is randomly sielected for epigenetic
silencing
○ NO transcription from the silenced X chromosome
○ Silenced chromosome forms a condensed, transcriptionally inactive mass in
nucleus of femal somatic cells = Barr body
● If one chromosome wasnt silenced you would have double the dosage BUT the
dosage between males and females is the same due to X-inactivation.

● Yellowish green could = X-chromosome (active)

● Condensed yellow = heterochromatin, silenced X-chromosome
● If DNA is active is accessible to transcription factors and transcriptionally active

XX females are genetic mosaics!

 ● The X selected for silencing in one cell is not the same as another cell necessarily
● Ignore the top (mice)
● Haplloid oocyte fertilized by a haploid sperm
● At the beginning of development, both X chromosomes are active
● Xa = active X xi=inactive X
● At some point during the blastocyst stage, one of the X-chromosomes gets silenced
● There is a small population (primordial germ cells - cells destined to become oocytes in
the XX female0 - green cluster on the top right of the blastocyst

● Suppose a cell has 2 X-chromosomes X1X2

● Black = inactive X1 (and active X2)
● Green = active X1 (and inactive X2)
● The choice of which X chromosome will be inactivated in each cell is random!
● Some cells with an active X1 and some cells with an inactive X1

X-inactivation: Tortoiseshell cat

● Gene responsible for fur colour on X chromosome
𝐵
● 𝑋 = orange
𝑏
● 𝑋 =black
● Male cats: No X-inactivation = either orange or black
● Female cats: One chromosome is inactivated
 ○ Homozygous = either black or orange
○ Heterozygous = Mosaic fur coat

○
●

X-inactivation & the inheritance of disease-causing alleles

● Which chromosome gets silenced = random

● Heterozygous might show symptoms of phenotype
● Since there is a combination of cells in females, they usually wont express the
phenotype as much as males (2 X-chromosomes so mutation is not as bad if its only on
one).
● In males, if they inherit the X impacted by the mutation then they will be affected by the
phenotype =phenotype is more severe in males since they only have one copy
○ Why we see colourblindness more in men than women (x-linked)

X-inactivation and the inheritance of disease causing alleles

A) Normal
● Healthy cells have two unaffected/normal copies of the X chromosome, which
may carry homozygous or heterozygous alleles for X-linked genes
● Each cell has one X chromosome that is epigenetically silenced (arrows)
 B) Disease-causing mutation in X-linked gene:
● In biological females (XX-individuals)
● If mutation is heterozygous
○ X-linked recessive = the process of normal/healthy X in non-silenced
cells is sufficient for normal tissue function
○ X-linked dominant = the presence of normal/healthy X in non-silenced
cells is insufficient for normal function
● If mutation is homozygous
○ All cells will be affected even with X-inactivation
○ In biological males (or XY-individuals)
○ All cells will be affected since only one copu of the X chromosome) more
severely affected)

Examples of X linked disorders

X-linked disorders - Hemophilia

● Hemophilia A: deficiency in clotting factor VIII (8)
○ (approx 1/5000 births)
● Hemophilia B: deficiency in clotting factor XI
○ Approx 1/20 000 births
 ○

● Males only inherit their X from their mother

● X-linked recessive pattern
● All affected sons, all mothers are carriers

Sex linked traits: final thoughts

● Genes on the PAR regions of the X-chromosome escape silencing
○ The pair of alleles would act likethose on autosomes, i.e., heterozygous may
mask recessive alleles
● In X-linked dominant inheritance, more females than males will express the disease
phenotype, but usually will have a milder clinical course than males with the mutation
○ If it is fatal - you wont see too many meales with the condition (cuz they would
die from it?) ?
Sex and gender - let’s unlearn and relearn together
● Is it a BOY or a GIRL ?
● Gender reveal party = a celebration where an expectant mother shares/discovers the
assumed gender of her baby, based on the baby’s genetilia (revealed during ultrasound)

Sex vs. gender

● Gender is used to describe the characteristics of women and men that are socially
constructed, while sex refers to those that are biologically determined
● Peple are born female or male, but learn to be girls and boys who grow into women or
men. This learned behaviour makes up gender identity and determined gender roles
○ World Health organization, Europe
The gender binary: A Western social construct?
● Historically: biological sex (XY or XX) = gender (boy or girl or man or woman)
● Non-binary people fo not identify as either gender despite their biological sex
● Transgender people identifyy with the gender opposite ot that which has been
historically assigned to their biological sex
● Many other cultures recognize that there are more than only two genders (eg. Pakistan,
India, North American Indigenous groups)

Does the binary apply to biological sex?

● Yes!
● Intersex epople exist

Sex determination in humans

● Determined by the inheritance of the X or the Y chromosome from the father
● Presence of absence of the sex determining region of Y (SRY) gene (withihn the
differential region of the Y chromosome)
 ○ Determines testes deelopment
● SRY = male
● NO SRY = female
Sex reversal in humans
● Sex reversed XX males: often have a part of the Y including the SRY gene on their X
chromosomes
● Sex-reversed XY females frequently lack SRY on their Y chromosome either because it
has been replaced by part of the X chromosome, or because it has been inactivated by
mutation

- Unequal crossing over - SRY gene is so close to the PAR region so sometimes we have
swapping of the SRY gene onto the X chromosome - uunequal crossing over during
meiosis
- These individuals will show characteristics typical of XY individuals

Intersex individuals and atypical sex chromosome arrangements

● Intersex individuals show physical and or physiological characteristics of both sexes
● Possible causes:
○ Sex chromosome mutations (eg. loss of androgen sensitivity due to X-linked
recessive mutation of the andorgen receptor)
○ Sex chromosome aneuploidy (atypical number of sex chromosomes)
■ XXY (Klinefelter’s syndrome)
■ XYY (Jacob’s syndrome)
■ XO (Turner Syndrome)