Lecture 7

Question 1

What is the primary sex ratio (conceived)/ secondary sex ratio (born)? and why?

Answer 1

120-160 males/ 100 females 106 males/ 100 females why? Maybe Y chromsome lighter as it’s smaller than X so sperm with Y swims faster- not proven! Males survive less often, around 19 yrs ratio is 1:1 and at 70 62 males/ 100 females

Question 2

What is a reciprocal cross?

Answer 2

-to discover if it’s X linked disorder - both of the parents should be purebreeding, in one get the male affected in the other female affected and observe the phenotypic ratios, if different= sex linked because males only get Y from dad! -if the disorder recessive and the mother has it, all the male offspring will have it - if it were autosomal the phenotypic ratios are the same in both male affected x normal female and vice versa

Question 3

Can X-linked disorders be passed from father to son?

Answer 3

-never any transmission of X linked disorder from father to son since son only gets Y from the father

Question 4

When can females get X-linked disorders?

Answer 4

• females can only be affected if father affected

Question 5

How is colourblindness inherited?

Answer 5

X linked dominant, no homologous gene on Y
C-normal vision
c-colour blind

females can be XCXC(normal) XCXc (carrier female) XcXc (colourblind)
males can be XCY (normal) XcY (colourblind) - males are hemizygous
if parents XCXc and XCY- ¼ chance of it being colournlind for a male, no chance for a daughter
if parentXCXc XcY- ¼ chance for both son and daughter

Question 7

What is a major worry for haemoophiliacs?

Answer 7

• cutting yourself and bleeding out, not a major issue, spontaneous bleeding in the joins (painful) is
• factor VIII manufactured today so you can inject it at home, either keep levels up or inject after injury

Question 8

Describe the process of blood clotting.

Answer 8

-if you don’t have factor VIII can’t convert fibrinogen to fibrin

Question 9

What is Haemophilia A?

Answer 9

= deficiency of Factor VIII
= severe impairment of clotting – the worse haemophilia 7x as common than B

Question 10

What is Haemophilia B?

Answer 10

= Christmas disease
= deficiency of Factor IX
= mild impairment of clotting (better haemophilia, not as bad)

Question 11

How do we do a reciprocal cross if the female is hetrogametic?

Answer 11

-reciprocal crosses are reversed, the transmission is father to daughter (e.g. parrots Budgerigars, albino)

Question 12

How was X inactivation discovered?

Answer 12

• for an X linked trait females have twice the gene product of a male (have two Xs)
• 1949 dark staining body on the perimeter of interphase cells in females discovered by Murray Barr
• not seen in males
• 1961 Mary Lyon proposes it’s an inactive X chromosome
• tested on females with XXX- then two bodies, XXXX- three bodies, always only one X switched on

Question 13

When is on eof the Xs in a female switched off?

Answer 13

• in early embryonic development of a female
• happens after 15-16 days of gestation (blastocysts stage) till then both switched on- so women not colourblind etc

Question 14

Which of the Xs switches off, from mother or from father?

Answer 14

-random in humans, can be the one from father or from the mother

-1 switches off randomly and the same one is deactivated in all the cells emerging from that particular
cell

Question 15

Why is one of the Xs switches off?

Answer 15

dosage compensation to equalize gene product between males and females, then both have the same number of protein product coming from the X chromosome

Question 16

Is the X also switched off in oocytes?

Answer 16

the X inactivation reverses in the oocytes so mother can pass on both X and X

Question 17

How do we get female mosaics?

Answer 17

if female heterozygous for something and different Xs switch off in different parts= mosai

Question 18

Give two example s of moasaics.

Answer 18

e.g. Anihidrotic ectodermal dysplasia- sweat glands, hair follicle undeveloped in parts of the body

e. g. Heterozygous (XOXB O-orange, B-black) female cat is a mosaic- that’s why they have different colour is different parts of the body, it depends on where the X’s have switched off, the earlier the switching the bigger the colour patches
- the only way for a male tortoiseshell(the color patches) is Klinfelter XXY (have two Xs so can get it)

Question 19

What is XIST?

Answer 19

• XIST (X inactivation specific transcript)= a gene locus on the X chromosome which is only transcribed from the inactivated X)
• expression of XIST on the active X is suppressed by methylation

Question 20

What is the process of X inactivation (XIST) 4 steps:

Answer 20

1. The XIST gene is on the X chromosome
2. Transcription of the XIST gene makes an interference RNA(interferes with gene expression)
3. The RNA binds to the X chromosome from which it was transcribed, coats it
4. Recruits other proteins that condense the chromatin by methylation and histone deacetylation to heterochromatin

Question 21

Are all of the genes on the inactivated X switched off?

Answer 21

-some genes in the pseudoautosomal region (homologous sequences of nucleotides on the X and Y chromosomes, crossing over mostly there, allows for segregation in meiosis in males and so the X and Y are properly aligned) remain active, that allows explanation for Turner’s etc.

Question 22

What is lyonisation?

Answer 22

X inactivation

Question 23

What is atypical lyonisation?

Answer 23

• manifesting heterozygote
• when a heterozygous mammal female she is a mosaic

e.g. female XHXh (h-haemophilia A)
so if 50% of XH and 50% of Xh switch off enough normal factor VIII to have normal clotting
if 20% XH remain and 80% Xh remain= mild haemophilia
so if 50% and more of the disorder cells= showing some signs!

Question 24

What is Duchenne Muscular Dystrophy?

Answer 24

• heterogenous (lot of genes involved) X linked condition
• very severe, patients are losing dystrophin in their muscles
• death in late teens to early twenties
• never female with full blown condition but can have mild forms if heterozygous, die before reproducing