Genetics :(

Question 1

Define congenital

Answer 1

Any abnormality present at birth, whether due to a genetic disease or not.

Question 2

Define Consanguinity

Answer 2

Reproductive union between two blood relatives

Question 3

What proteins does DNA wind around?

Answer 3

Nucleosomes (made up of approx 8 histones)

Question 4

What are Robertsonian chromosomes?

Answer 4

Chromosomes that lack a p arm (pairs 13,14,15,21,22)

Question 5

Describe a chromosome

Answer 5

p arm (short) and a q arm (long) joined by a centromere

Question 6

What are the 3 human genomes?

Answer 6

Somatic, germline, mitochondrial

Question 7

When are changes to the genome heritable?

Answer 7

When the changes are in the germline or mitochondrial genome.

Question 8

What is a mutagen?

Answer 8

Exposure to a substance damages the DNA base sequence and causes a mutation. Can be in the womb or post-natal. E.g. radiation

Question 9

What is a teratogen?

Answer 9

Exposure to a substance damages embryo or fetal development, can also be a mutagen if DNA is damaged. E.g. alcohol, viruses

Question 10

What is a mendelian mutation?

Answer 10

A monogenic mutation, where a single mutation on a gene is causing disease.

Question 11

What is a somatic mutation?

Answer 11

The mutation causing disease is found only in the affected tissue.

Question 12

What is a de novo mutation?

Answer 12

The variant occurs first in the germ line/ zygote so is present in offspring but not parents’ somatic genome, so wasn’t heritable.

Question 13

What is dosage sensitivity?

Answer 13

Many genes are dosage sensitive so that deletion or duplication of genetic material causes an imbalance and results in disease.

Question 14

Define benign variant

Answer 14

Gene variant known to have no impact on health.

Question 15

What are the two types of chromosome translocations?

Answer 15

Balanced (no gain or loss of material)
Unbalanced (loss or gain of material, results in genetic conditions)

Question 16

What causes down syndrome?

Answer 16

Trisomy 21 - an extra copy of all or some of chromosome 21.

Question 17

What causes Edwards syndrome?

Answer 17

Congenital condition caused by trisomy 18.

Question 18

What is autosomal dominant inheritance?

Answer 18

Disease occurs in the heterozygous state (variant on only one gene). Tends to cause a gain of (toxic) function.
It has a 50% recurrence risk.

Question 19

What does an autosomal dominant pedigree look like?

Answer 19

M/F affected in equal proportions
Multiple generations affected
Both genders can pass on to either gender of offspring.

Question 20

Define penetrance

Answer 20

% of individuals with the variant that develop the medical condition.
Can be age related (used in preventative medicine)
some variants have higher than others
some individuals never develop the condition

Question 21

Define variable expressivity

Answer 21

Same variant causing different symptoms /signs in different people.

Question 22

Anticipation

Answer 22

The condition manifests in successive generations earlier or with more severe symptoms.

Question 23

What is autosomal recessive inheritance?

Answer 23

Occurs in homozygous state, tends to cause loss of function

Question 24

What does an autosomal recessive pedigree look like?

Answer 24

M/F affected in equal proportions
Affected individuals only in one generation
Parents could be related

Question 25

Carrier parents seeking advice

Answer 25

25% recurrence risk from 2 carrier parents, 2/3 chance being a carrier if affected sibling
Carrier frequency of recessive conditions varies in different populations due to culture, environment, location

Question 26

Difference between X-linked recessive and X-linked dominant

Answer 26

recessive: unaffected female carriers, affected males
dominant: both M/F affected

Question 27

Gonadal mosaicism

Answer 27

Mutation only found in ovary(germline?) and not in the blood DNA
Two different populations of cells in the gonads.
No clinical tests but prenatal tests

Question 28

How to recognise multifactorial inheritance

Answer 28

Risk of condition (and incidence) much higher if relatives have it, greatest for 1st degree relative
Decreases rapidly in more distant relative
>1 affected relative increases risk for other relatives
Liability - genetic and environmental causation combined

Question 29

Somatic mosaicism

Answer 29

Some tissues have the variant and some do not due to mutations occurring in the zygote, also cancer.

Question 30

2 types of mitochondrial disease?

Answer 30

Homoplasmy - all mitochondria in the cell have the same genetic code
Heteroplasmy - certain proportion of mitochondria in a cell has a genetic variant
Always passed down from the mother

Question 31

Imprinting disorders

Answer 31

Some genes are only active on the maternal or paternal copy (other is inactive).
Deletion if the active gene can cause disease

Question 32

Synonymous mutation

Answer 32

Variant causes no change in the amino acid sequence

Question 33

Non synonymous mutations

Answer 33

Missense - alters one amino acid (most common NS mutation)
Loss of function -(least common) IN FRAME shift multiples of 3 nucleotides are inserted/deleted - OUT OF FRAME shift non-multiple of 3, all codons change after variant, nonsense mediated decay occurs
Splice site - intron is translated into protein

Question 34

Copy number variants

Answer 34

Deletion or duplication of a segment of chromosome

Question 35

Trinucleotide repeat expansion

Answer 35

Repeats are duplicated or deleted X times
Form an elongated, toxic mRNA which resists degradation
occurs in non-coding DNA
e.g. huntingtons

Question 36

Comparative genomic hybridisation

Answer 36

Probe binds to section on DNA
Different dye released if section isn’t there
Can detect CNVs

Question 37

Genome test vs Exome test

Answer 37

Genome detects copy number variants, splice sites, trinucleotide repeats, promoter region
Exome detects mosaic variants, genome can miss them, exome is quicker

Question 38

Why trio test?

Answer 38

picks up de novo variants, good for determining pathogenic(several ppl in family have variant and disease) vs benign variants(variant in unaffected patient and common in general population)

Question 39

Predictive genetic testing

Answer 39

Adult can’t request test on child
For adult without symptoms for highly penetrant disease, seen as promoting autonomy

Question 40

Prenatal diagnosis

Answer 40

Should only be done for a ‘serious genetic condition’ but what is in this category?
Could lead to genetic modifications, ending pregnancies

Question 41

Preimplantation genetic testing

Answer 41

Pick embryos without genetic disease before putting into the womb

Question 42

Direct to consumer testing

Answer 42

Quick online ordered tests, cheap, no counselling advice or other services
Costs the NHS as it misses out a lot of context