Clinical Genetics

Question 1

Amyloid Precursor Protein: percentage of EOAD? chrosomome?

Answer 1

10-15%. Chromosome 21.

Question 2

Presenelin 1: percentage of EOAD? chromosome?

Answer 2

30-70%. Chromosome 14.

Question 3

Presenelin 2: percentage of EOAD? chromosome?

Answer 3

5%. Chromosome 1.

Question 4

Which early onset alzheimers disease gene do downs syndrome patients have an extra copy of?

Answer 4

Amyloid Precursor protein

Question 5

What gene is implicated in late onset alzheimers?
What is the risk for hetero and homozygotes?
What chromosome is it on?

Answer 5

Apolipoprotein E (APOE)
Hetero: 3x inc risk. Homo: 10-30x inc risk.
Chromosome 19.

Question 6

What genes are implicated in schizophrenia?
on chromosome 1
on chromosome 6
chromosome 8
chromosome 22

Answer 6

DISC1
dysbindin
neuroregulin
COMT

Question 7

What other condition is involved in chromosome 22?

What defects does such a person have?

Answer 7

In digeorge/velocardiofacial disorder, chromosome 22 is deleted. 
Cleft palate
Abnormal facies
Thymic hyperplasia 
Cardiac abnormalities (Tetralogy of Fallot)
Hypocalcaemia/hypoparathyroidism
2
2

Question 8

What base pairs pair up in DNA?

RNA?

Answer 8

Adenine - Thymine
Guanine - Cytosine
Swap Thymine for Uracil in RNA

Question 9

In ADHD Heritability -
What is the number quoted for heritability?
Difference between males and females?
Two genes involved?

Answer 9

0.7-0.9 (74%)
No difference
DAT1, DRD4

Question 10

Autism Heriability -
Siblings more likely? by what percentage?
mono twins concordance?
hetero twin concrodance ?

Answer 10

50-100% more likely
76%
34%

Question 11

What gene is associated with FTD with Parkinsons?

Answer 11

MAPT

Question 12

What gene is associated with CADASIL?

Answer 12

NOTCH3

Question 13

What gene is associated with Huntingdon’s?

Answer 13

IL15 (Huntingdin gene)

Question 14

What is the recombination fraction?

Answer 14

‘a measure of the distance between loci’

The recombination can vary from 0% if they are extremely close to 50% if they are on different chromosomes

Question 15

What is LOD Score?

Answer 15

The LOD score (logarithm of the odds) is a method used to ascertain if there is evidence for linkage.

Question 16

Name 4 Autosomal Dominant conditions.

Chance of child of affected parent getting it?

Answer 16

Achondroplasia.
Huntingdons.
Neurofibromatosis.
Marfans.
50%

Neurofibromatosis type 1 and 2, tuberous sclerosis, achondroplasia, Huntington disease, Noonan’s syndrome

Question 17

Name 3 Autosomal Recessive conditions.

Answer 17

Phenylketonuria
Wilsons
Homocystinuria

Phenylketonuria, homocystinuria, Hurler’s syndrome, galactosaemia, Tay-Sach’s disease, Friedrich’s ataxia, Wilson’s disease, cystic fibrosis

Question 18

Name 2 conditions passed on by mitochondial

Answer 18

Leber’s hereditary optic neuropathy, Kearns-Sayre syndrome

Question 19

X-Linked recessive

Answer 19

Cerebellar ataxia, Hunter’s syndrome, Lesch-Nyhan
Duchenne muscular dystrophy
Red green colour blindness
Hemophilia A and B

Question 20

X-Linked dominant

Answer 20

Vitamin D resistant rickets, Rett syndrome

Question 21

What chromosome is affected in Hungtingdons?
What decades usually affected?
EEG?
Chief path findings?

Answer 21

4
3rd and 4th decade of life
Flattened trace
Atrohpy of caudate and putamen (hence chorea), temporal lobe (hence memory issue), frontal (hence executive function)

Question 22

Types of mutation meaning:
MISSENSE
Nonsense
Point 
Frame shift
Silent

Answer 22

MISSENSE = new amino acid created
Nonsense = stop codon made
Point = simple change
Frame shift = insertion or deleiton
Silent = same amino acid made

Question 23

What conditions are affected by chromosome 1 issues?

Answer 23

Presenelin 1 gene (EOAD)

DISC1 (implicated in schizophrenia)

Question 24

What conditions are affected by chromosome 4 issues?

Answer 24

Huntingdons. CAG repeat.

Also Wolf-Hirschlon (4p; helmet warrior)

Question 25

What conditions are affected by chromosome 5 issues?

Answer 25

5p deletion (cri-du-chat)

Question 26

What conditions are affected by chromosome 9 issues?

Answer 26

Tuberose sclerosis

Question 27

What conditions are affected by chromosome 15 issues?

Answer 27

``` Prader Wili (paternal) Angelmans (maternal) displaying genomic imprinting ```

Question 28

What does heritability mean?

Answer 28

Heritability is the proportion of phenotypic variance attributable to genetic variance. This means that if a condition has a heritability of 0.80 then 80% of the variance of that condition seen in a population is attributable to genetic variation. The remaining 20% is attributable to environmental factors.

Question 29

What are the top three and bottom three for heritability?

Answer 29

Bipolar 90 Autism 90 Schizophrenia 85 ADHD 80 Anorexia 55 Alcohol dependence 50 Depression 35

Question 30

What tauopathies do you know

Answer 30

Alzheimer's Pick's (frontotemporal dementia) Progressive supranuclear palsy Cortiocobasal degeneration

Question 31

What chromosome codes for tau?

Answer 31

Chromosome 17

Question 32

``` What is the trinucleotide repeat present in Huntingdons? Normally how many times repeated? What decade does disease manifest? EEG? Macroscopic findings? ```

Answer 32

CAG Usually less than 27 times Usually 3rd or 4th decades but can be earlier if more repeats Flattened trace Atrophy in caudate/putamen (hence chorea), frontal lobe (hence executive function issues), temporal regions (hence memory impairment)

Question 33

What term terms disorders with trinucleotide repeat disorders? What conditions meet this?

Answer 33

Dynamic. Huntingdons, spinocerebellar ataxia- CAG Myotonic dystrophy CTG Fredreichs ataxia (GAA) Fragile X CGG

Question 34

Go through the stages of mitosis (cell division)

Answer 34

Interphase: Gap 1 S phase (synthesis of DNA/DNA replication) Gap 2 Mitotis: Prophase - Chromatin condenses and becomes visible as chromosomes Prometaphase - The nuclear membrane dissolves and microtubules become attached to the centromeres Metaphase - Chromosomes become aligned at the middle of the cell Anaphase - Paired chromosomes separate and begin moving to opposite ends of the cell Telophase - Chromatids arrive at opposite poles of the cell and new nuclear membranes begin to form around them Cytokinesis - The cell splits into two daughter cells each with a nucleus

Question 35

What is an endophenotype? | What criteria do they have to fulfill?

Answer 35

An endophenotype is a heritable marker for a condition that is invisible to the naked eye and relies on some form of laboratory measurement. It is associated with illness in the population It is heritable It is state independent (present whether or not disease is present) Within families, endophenotype and illness co-segregate (the endophenotype is more prevalent among ill relatives of ill probands than healthy ones) The endophenotype found in affected family members is found in non affected family members at a higher rate than in the general population.

Question 36

What is the Heidy-Weinberg Principle?

Answer 36

The Hardy-Weinberg Equation is used to predict the percent of a human population that may be heterozygous carriers of recessive alleles for certain genetic diseases. No mutations must occur, so that new alleles do not enter the population. No gene flow can occur (no migration of individuals into, or out of, the population). Mating between individuals must be random ( individuals must pair by chance). Population must be sufficiently large that no genetic drift (random chance) can cause the allele frequencies to change. Differences in genotype do not confer disparate survival or reproductive success on an individual (no natural selection occurs).

Question 37

Fragile X vs Klinefelters | Big differences?

Answer 37

Fragile X Passed on X chromosome Elongated face, large ears, large testicles, hand flapping, shyness, and little eye contact Klinefelters extra X - XXY infertile Tend to be tall with small testicles. Typically introverted with poor social and school performance

Question 38

What is meiosis? | In what phase do you get genetic recombination?

Answer 38

``` Meiosis is a special type of cell division necessary for sexual reproduction. Prophase I (homologous recombination) ```

Question 39

In what condition do you get elfin like features?

Answer 39

Williams. | 7q11 deletion

Question 40

Which are the purine bases? | The pyrimidine ones?

Answer 40

AG | CTU

Question 41

What type of pass down follows knights move inheritance? | What conditions come under this bracket?

Answer 41

X-Linked Recessive. Duchenne muscular dystrophy Red green colour blindness Hemophilia A and B

Question 42

What is lyonisation?

Answer 42

- To correct the imbalance of possibly getting two Xs from Mum, by way of the process called Lyonization (X-inactivation), females transcriptionally silence one of their two Xs. - The inactivated X chromosome, then condenses into a compact structure called a Barr body, which is maintained in a silent state.

Question 43

Give three traits of XYY individuals.

Answer 43

- usually asymptomatic, not usually infertile - taller than average - usually have learning disability

Question 44

In Rett syndrome - what kind of inheritance? - give some characteristic features.

Answer 44

X linked dominant. Chromosome 28. Normal for the first 12 months. Regression and loss of skills from around 18 months onwards. Hand-wringing movements are the most common feature.

Question 45

What kind of inheritance is also known as - Vertical - Horizontal - Knights move

Answer 45

Vertical: autosomal dominant Horizontal: autosomal recessive Knights move: x linked (recessive)

Question 46

``` Heritability of schizoprhenia for: Identical twins Both parents have it Fraternal twins Children Full sibling Half sibling Parents General popilation ```

Answer 46

``` Identical twins - 50% Both parents - around 50% fraternal twins - around 17% children - around 13% full sibling - around 9% half sibling around 6% parent around 6% ```