Missing X chromosomes and triple repeat disorders

Question 1

what regulates sex determination?

Answer 1

gene on short arm of Y chromosome - SRY gene

without it all embryos would develop as female

Question 2

what regulates sex determination?

Answer 2

gene on short arm of Y chromosome - SRY gene

without it all embryos would develop as female

Question 3

SRY gene expression

Answer 3

at 7 weeks gestation

causes production of androgens leading to development of male embryo

Question 4

what is karyotype?

Answer 4

an individuals collection of chromosomes

Question 5

XX male karyotype

Answer 5

SRY gene has been translocated onto the X chromosome by crossing over
causing a male embryo to develop but with 2 X chromosomes

Question 6

clinical features of XX male

Answer 6

small testes
sterile
ambiguous internal and external genitalia
male phenotypes

Question 7

SRY mutation

Answer 7

XY genotype with female phenotype

due to inactivation of SRY gene

Question 8

pseudoautosomal regions on X and Y chromosomes

Answer 8

2 regions
PAR 1 and 2 on X and Y chromosomes
help the 2 chromosomes align in meiosis and pair to allow recombination

Question 9

X chromosome aneuploidies affecting males

Answer 9

klinefelter syndrome
XYY syndrome
Y chromosome rearrangements

Question 10

X chromosome aneuploidies affecting females

Answer 10

Turner syndrome

Trisomy X syndrome

Question 11

Klinefelter syndrome karyotype

Answer 11

XXY

Question 12

clinical features of Klinefelter syndrome

Answer 12

taller and thinner than average
poor beard growth 
gynaecomastia
infertile 
defective spermatogenesis
small testes
reduced testosterone production 
reduced IQ
mostly lead a normal life

Question 13

epidemiology of Klinefelter syndrome

Answer 13

common - 1/1000
extremely rare forms = XXXY or XXXXY
common live birth
50% miscarriage risk

Question 14

Karyotype for XYY syndrome

Answer 14

XYY

Question 15

Karyotype for Y chromosome rearrangements

Answer 15

X del (Yq)

Question 16

Karyotype for Turner Syndrome

Answer 16

X
Xdel(Xp)
Xi(Xq)
X mar 
missing X chromosome

Question 17

Karyotype for Trisomy X syndrome

Answer 17

XXX

Question 18

clinical features of Turner Syndrome

Answer 18

short
no puberty
webbed neck
underdeveloped breasts
infertile
broad chest
widely spaced nipples
low IQ
normal life expectancy 
presents in mosaic form

Question 19

epidemiology of Turner syndrome

Answer 19

1/2500

spontaneous abortion is high

Question 20

what is mosaicism?

Answer 20

different cells in the body have different chromosome composition
this rescues missing X chromosome phenotype
the cells replicate the single X chromosome in some cells then form a normal line of cells

Question 21

SRY gene expression

Answer 21

at 7 weeks gestation

causes production of androgens leading to development of male embryo

Question 22

what is karyotype?

Answer 22

an individuals collection of chromosomes

Question 23

XX male karyotype

Answer 23

SRY gene has been translocated onto the X chromosome by crossing over
causing a male embryo to develop but with 2 X chromosomes

Question 24

clinical features of XX male

Answer 24

small testes
sterile
ambiguous internal and external genitalia
male phenotypes

Question 25

SRY mutation

Answer 25

XY genotype with female phenotype | due to inactivation of SRY gene

Question 26

pseudoautosomal regions on X and Y chromosomes

Answer 26

2 regions PAR 1 and 2 on X and Y chromosomes help the 2 chromosomes align in meiosis and pair to allow recombination

Question 27

X chromosome aneuploidies affecting males

Answer 27

klinefelter syndrome XYY syndrome Y chromosome rearrangements

Question 28

X chromosome aneuploidies affecting females

Answer 28

Turner syndrome | Trisomy X syndrome

Question 29

Klinefelter syndrome karyotype

Answer 29

XXY

Question 30

clinical features of Klinefelter syndrome

Answer 30

``` taller and thinner than average poor beard growth gynaecomastia infertile defective spermatogenesis small testes reduced testosterone production reduced IQ mostly lead a normal life ```

Question 31

epidemiology of Klinefelter syndrome

Answer 31

common - 1/1000 extremely rare forms = XXXY or XXXXY common live birth 50% miscarriage risk

Question 32

Karyotype for XYY syndrome

Answer 32

XYY

Question 33

Karyotype for Y chromosome rearrangements

Answer 33

X del (Yq)

Question 34

Karyotype for Turner Syndrome

Answer 34

``` X Xdel(Xp) Xi(Xq) X mar missing X chromosome ```

Question 35

Karyotype for Trisomy X syndrome

Answer 35

XXX

Question 36

clinical features of Turner Syndrome

Answer 36

``` short no puberty webbed neck underdeveloped breasts infertile broad chest widely spaced nipples low IQ normal life expectancy presents in mosaic form ```

Question 37

epidemiology of Turner syndrome

Answer 37

1/2500 | spontaneous abortion is high

Question 38

what is mosaicism?

Answer 38

different cells in the body have different chromosome composition this rescues missing X chromosome phenotype the cells replicate the single X chromosome in some cells then form a normal line of cells

Question 39

what is X inactivation?

Answer 39

most of the genes on the second X chromosome become inactivated in females = dosage compensation

Question 40

what is dosage compensation?

Answer 40

random process occurring early in embryogenesis, occurs by coating the X chromosome with RNA molecule so it becomes condensed and cannot produce any protein

Question 41

x chromosome vs Y chromosome

Answer 41

X contains 800 genes, but Y is gene poor

Question 42

what causes X inactivation?

Answer 42

Xist gene

Question 43

x-linked diseases

Answer 43

no male to male transmission predominantly affects males, as females protected by second normal X chromosome dominant conditions can affect females

Question 44

examples of x-linked diseases

Answer 44

Haemophilia A and B | Duchenne muscular dystrophy

Question 45

x-linked dominant inheritance

Answer 45

no male-to-male transmission females can be more often affected than males females less severely affected

Question 46

examples of x-linked dominant inherited conditions

Answer 46

Rett syndrome | fragile X syndrome

Question 47

Rett syndrome

Answer 47

``` delayed development from 1 year autism absent speech lose ability to walk de novo mutation predominantly affects girls because it is lethal in males ```

Question 48

Fragile X syndrome

Answer 48

``` causes developmental delay diagnosed early in childhood attention deficit autism seizures females less severely affected trinucleotide repeat disorder ```

Question 49

fragile X syndrome

Answer 49

trinucleotide repeat in FMR1 gene CGG repeats cause methylation of CGG and inactivates the FMR 1 gene looks like broken X chromosome under microscope

Question 50

number of CGG repeats

Answer 50

<55 healthy - 30 most common | fragile X syndrome = >200 repeats

Question 51

FMR 1 gene

Answer 51

on end of long arm of x chromosome

Question 52

what are trinucleotide repeat disorders?

Answer 52

unstable expansion during meiosis number of repeats increases with reproduction can be mediated by DNA, RNA or protein

Question 53

features of trinucleotide repeat disorders

Answer 53

some affect coding region | show anticipation

Question 54

CAG repeats

Answer 54

polyglutamine in proteins

Question 55

disorders caused by trinucleotide repeats

Answer 55

myotonic dystrophy huntington's >30 disorders

Question 56

what is anticipation?

Answer 56

increased clinical severity or younger age of onset in successive generations of disease - fragile X is an exception to this

Question 57

myotonic dystrophy

Answer 57

symptoms more severe and occur earlier further down the generations