SEX LINKAGE

Here Comes the Sun King• The tale of King Henry VIII and his six

wives

• Wives kept experiencing miscarriages

• AND COULD NOT GIVE BIRTH TO A HEALTHY MALE HEIR….

The wives of King Henry VIII

• Catherine of Aragon - divorced• Anne Boleyn - beheaded• Jane Seymour - died• Anne of Cleaves - divorced• Catherine Howard - beheaded• Catherine Parr - survived

• WERE THE wives TO BLAME? Who is to blame for gender determination? What could explain such misfortune?

http://www.nbcnews.com/id/42041766/#.UoqWb-JLovs

Rationale…

• GENDER DETERMINATION = MALE• If the sperm gamete that fertilizes is X –female

• If the sperm gamete that fertilizes is Y- male

• POSITIVE MEETS NEGATIVE?• Henry may have belonged to a rare blood group, called Kell positive.

Causes autoimmune reaction against baby if wife is not.

• X-linked McLeod syndrome too?• researchers propose that he also had a rare genetic disorder called

McLeod syndrome. Carried on the X-chromosome, the disease generally affects only men and usually sets in around age 40 with symptoms including heart disease, movement disorders and major psychological symptoms, including paranoia and mental decline.

Female and Male Sex Chromosomes

The X chromosome is much larger than the Y chromosome – it carries between 100-200 genes. Because both males and females have at least 1 X chromosome, important genes and information are found on the X chromosome. You can survive without a Y chromosome, but you can’t survive without an X chromosome!

1st Law: Law of Segregation

• Mendel’s law of segregation states that every individual possesses a pair of alleles and passes a randomly selected copy (one or the other) to its offspring.

The same happens for sex chromosomes

the SEX chromosomes also carry genes. We use the letters X and Y to identify these chromosomes.

Sex Chromosomes and X-Linked Traits

• SEX LINKED TRAITS – genes located on the sex chromosomes, usually the X chromosome.

• NOTE: It’s the sperm/male parent that determines the sex of a child. • The sex chromosomes do more than code for gender.

Thomas Hunt Morgan’s Flies

• Geneticist

• Studied fruit flies (Drosophila melanogaster)

• Context: 1908 – before anyone knew the link between chromosomes and heredity

• Drosophlia melanogaster are a model organism for genetics• -reproduces rapidly

• -can reproduce when they are only 10 to 15 days old

• -therefore can study many generations in a short time

• -small (many of them can be contained in a small vial)

• -males and females are easily distinguishable

• Won the Nobel Prize in 1933 for discovering that chromosomes carried heritable material

One day in the lab…• Examined eye colour in Drosophila

• Noticed the appearance of white eyed flies among many red eyed offspring

• Concluded the white eyes must be a mutation

• Wanted to do a breeding analysis to understand about white eyes

• Did a test cross

The test cross…• Mated white eyed male with purebred red eyed female (RR) and

found all F1 generation had red eyes

• According to normal Mendelian genetics, the red eyed allele was dominant

F1 F2

• He then decided to mate two of the F1 generation flies and got a 3:1 ratio of red to white in the F2

• Also seemed to support Mendelian genetics

•  EXCEPT no females has white EYES!!

So he crossed themMaybe white

eyes are lethal in females?

So he crossed them

I guess not….but what does this have

to do with sex?

Morgan’s Results• The appearance of white eyes in

females shows that this trait is not lethal in females.

• All possible combinations of white eyes and sex are possible.

• The white-eye trait can be carried over to females when F1 females are crossed with white-eyed males.

Did it have to do with chromosomes?

• The male and females seemed to have slightly different chromosomes

• Morgan found that the gene for white eyes seemed to follow the inheritance of sex

• From these and other crosses, he was able to figure out that genes were carried on chromosomes!

Recall: Chromosome Structure• Each human cell has

46 chromosomes• 23 pairs in total

• 22 are autosomes (not sex chromosomes)

• 1 pair of sex chromosomes

• Each pair is homologous (similar but not the same)

Females have two X chromosomes, (XX)Males have one X and one Y Chromosome (XY)

Sex Linked Inheritance

• Autosomal inheritance: inheritance of alleles located on autosomal (non-sex) chromosomes• (This is all the inheritance we have dealt with up until now)

• Sex-linked: describes an allele that is found on one of the sex chromosomes (X or Y)

•Aa, CDCd XHXh XHY

Hemizygous

• Just like before, females can be homozygous or heterozygous for a trait

• XHXh or XHXH

• Males are called hemizygous because they are neither heterozygous nor homozygous. They only have one possibility!

• XHY

Morgan’s Flies Re-examined

Purebred red eyed female is crossed with a white male

(NOTE: no symbol for eye colour on the Y chromosome because it does not carry an allele for eye colour)

The F2 generation…

Red Eye Females????• Can white eyed females possible occur in nature?

• YES! For this to happen, the offspring would have to inherit two recessive white eyed genes (therefore male must be white eyed (XrY) while female had at least one white eyed gene (XR Xr)

P: XRXr x XrY

Phenotype: 1 normal female: 1 white eyed female; 1 normal male: 1 white eyed male

Genotype: 1XR Xr : Xr Xr :XRY: XrY

Sex-Linked Disorders• Example of X Linked Genes: (Genes on located on the X

chromosome)

• Hemophilia (the inability to clot blood) • XhXh or XhY

• Myopia (nearsightedness) • XmXm or XmY

• Night blindness • XnXn or XnY

• Male Pattern Baldness • XbXb or XbY

• Colour-blindness• XcXc or XcY

Recessive X-linked

• All the above mentioned traits are recessive.

• Autosomal: You require 2 copies of the recessive allele to show the recessive trait (Ie: Blue eyed individuals have the genotype: bb) and having at least 1 copy of the dominant allele causes the dominant trait to be expressed. (Ie: The genotype Bb would result in a brown eyed individual)

• Sex linked traits: since males have only 1 X chromosome, they only require 1 copy of the recessive allele to show a recessive trait (____XhY_____). Females require 2 copies of the recessive allele to show a recessive trait (____XhXh____).

Carrier• Carrier: someone who does not have the phenotype of a

condition but has the allele for the condition.

• This usually applies to recessive genes

• For sex-linked genes, only FEMALES can be carriers.

• Males only have one copy of the allele, so they cannot be carriers. If they have the gene, they will express it.

Red Green Colour Blindness

• Inability to distinguish between red and green

• A red green colour blind person does not see the number 29 on the right

• In humans normal vision is completely dominant to red-green colour blindness

Muscular Dystrophy XdXd or XdY

• Skeletal muscles lose their normal structure and fibrous tissue develops in their place

• Caused by a recessive allele carried on the X chromosome and is sex-linked

Sex Linked Problems

• For example, hemophilia A is a blood disease where it takes a long time for the blood to clot. The gene for hemophilia is located on the X chromosome and is recessive.

• If a woman carrying the hemophilia allele marries a man who does not have hemophilia, what are the odds their children will have hemophilia?

How does it work• Let XH represent the normal allele

• Let Xh represent the allele for hemophilia

• (Y is the Y chromosome)

Results

• 50% of the males are affected

• 0% of the females are affected, although one is a carrier

Sex-Linked Genes

• Male Pattern Baldness• Located on the X chromosome

• Recessive

• If you are male and your mothers father had it, you may get it. It is rare in females.

• Why?

Male Pattern Baldness - P• Let XB represent the normal hair allele, and Xb represent

the baldness allele

• P - Normal Female x Bald Male

XBXB x XbY

Both sons are normal, both daughters are carriers!

Xb Y

XB XBXb

Carrier FemaleXBYNormal Male

XB XBXb

Carrier FemaleXBYNormal Male

Male Pattern Baldness = F1• F1 - Carrier Female x Normal Male

XBXb x XBY

100% of females are normal, ½ of sons are normal, ½ of sons are affected

Altogether, ¼ of children are affected

XB Y

XB XBXB

Normal FemaleXBYNormal Male

Xb XBXb

Carrier FemaleXbYAffected Male

What about a bald female?

It could happen, but you’d need

Bald or Carrier Female x Bald Male

XbXb or XBXb x XbY

There are also Y-linked diseases

• Obviously, only males can get it.

• If your dad has it, you will get it

• Less common because the Y chromosome is smaller and has less genes

Example 1

• In fruit flies, the gene for eye colour is X-linked. Red eyes are dominant to white eyes.

• If a heterozygous red-eyed female mated with a red-eyed male, what is the probability of a) Producing a white eyed offspring?

b) Producing a white eyed male offspring?

c) Producing a white eyed female offspring?

d) A male being white eyed?

Answer 1

• P: XRXr x XRY

Example 2

• What is the probability of a homozygous red-eyed female and a white eyed male having a carrier female offspring?

P: XRXR x XrY

Example 3

• What are the phenotypic and genotypic ratios when a white eyed female mates with a red eyed male?

P: XrXr x XRY