genetic factors & disease

Question 1

what are the 3 main groups of professionals in NHS clinical genetics

Answer 1

consultant clinical geneticists (physicians)

genetic counsellors (STP route)

laboratory and bioinformatics staff

Question 2

what is the genomic test directory

Answer 2

A directory that specifies which genomic tests are commissioned by the NHS in England, the technology by which they are available and the patients who will be eligible to access each test.

Question 3

what are the 3 causes of disease

Answer 3

genetic
multifactorial
environmental

Question 4

4 examples of genetic diseases

Answer 4

down syndrome
cystic fibrosis
Huntington disease
heamophilia

Question 5

4 examples of multifactorial diseases

Answer 5

spina bifida
cleft lip/palate
diabetes
schizophrenia

Question 6

what environmental factors cause disease (4)

Answer 6

poor diet
infection
drugs
accidents

Question 7

define genotype

Answer 7

genetic constitution of an individual

Question 8

define phenotype

Answer 8

Appearance of an individual which results from the interaction of the environment and the genotype

Question 9

define allele

Answer 9

One of several alternative forms of a gene at a specific locus;
* normal allele is also referred to as wild type
* disease allele carries the pathogenic mutation

Question 10

define polymorphism

Answer 10

frequent hereditary variations at a locus. Doesn’t cause problems (thats mutations).
Polymorphisms can make you more/less efficient or make you more/ less susceptible to disease.

Question 11

define genomics

Answer 11

study of the entirety of DNA, the genome, together with the technologies which allow sequencing, interpretation and analysis

Question 12

define genomic medicine

Answer 12

application of genomics to clinical care

Question 13

define gene

Answer 13

a segment of DNA that contains the biological instructions for a particular polypeptide

Question 14

define pathogenic variant

Answer 14

an alteration in genetic sequence that increases an individual’s susceptibility or predisposition to a certain disorder

Question 15

define benign variant

Answer 15

an alteration in genetic sequence which is not disease causing

Question 16

define variant of unknown significance

Answer 16

an alteration in a genetic sequence whose association with disease risk is unknown

Question 17

define secondary findings

Answer 17

results which provide information about variants which are unrelated to the primary reason or clinical indication for testing

Question 18

define additional looked for finding

Answer 18

results which provide information about variants which are unrelated to the clinical indication for testing; patient opts in and consents to testing for these

Question 19

define penetrance

Answer 19

the proportion of individuals with a particular genotype who express the associated phenotype/develop features of a condition

Question 20

define complete penetrance

Answer 20

gene or genes for the trait are expressed in all the population

Question 21

define incomplete penetrance

Answer 21

the genetic trait is only expressed in parts of the population

Question 22

define diagnostic testing

Answer 22

genomic/genetic testing in someone affected with features of a condition to aid diagnosis

Question 23

define predictive testing

Answer 23

genomic/ genetic testing in an unaffected individual, specifically for a pathogenic variant known to be present in a family member

Question 24

define homozygous

Answer 24

both alleles are the same at a locus

Question 25

define heterozygous

Answer 25

both alleles at a locus are different

Question 26

define hemizygous

Answer 26

only one allele refers to a locus on an X chromosome in a male

Question 27

what are the ACMG criteria

Answer 27

a formal scoring system to decide if a gene variant is “pathogenic”

Question 28

define consanguinity

Answer 28

reproductive union between two relatives

Question 29

define autozygosity

Answer 29

homozygous by descent i.e. inheritance of the same mutant allele through two branched of the same family

Question 30

define variable expression

Answer 30

Variation in clinical features (type and severity) of a genetic disorder between individuals with the same gene alteration

Question 31

define sex limitation

Answer 31

Expression of a particular characteristic limited to one of the sexes

Question 32

define multi factorial condition

Answer 32

Diseases due to a combination of genetic and environmental factors. If the condition is more common in one particular sex, the relatives of an affected individual of the less frequently affected sex will be a higher risk than relatives of an affected individual or the more frequently affected sex i.e if a boy has the condition then female relatives are more at risk and vice versa.

most common diseases are multifactorial

Question 33

define late onset

Answer 33

Condition not manifested at birth (where it does this is called congenital). Classically adult-onset e.g Huntington’s

Question 34

how do you recognise rare disease in primary care

Answer 34

G: group of congenital anomalies
E: extreme presentation of common conditions
N: neurodevelopmental delay or early onset neurodegeneration
E: extreme pathology
S: surprising laboratory values

Question 35

what is the classification of genetic disease

Answer 35

• chromosomal
• mendelian - autosomal dominant, autosomal recessive, X linked
• non traditional - mitochondrial, imprinting, mosaicism

Question 36

what is autosomal dominant inheritance

Answer 36

mendelian
disease which is manifest in the heterozygous state
Affects both males and females in equal proportions.
Affected individuals in multiple generations.
Transmission by individuals of both sexes to both sexes.

Question 37

what chance is there of offspring having a condition with autosomal dominant

Answer 37

50%

Question 38

how many defective genes do you need for autosomal dominant

Answer 38

only 1

Question 39

what is the only way to pass on autosomal dominant

Answer 39

male to male

Question 40

why are sometimes both parents unaffected in autosomal dominant

Answer 40

three reasons:
- most commonly they don’t have the genes for it
- gonadal mosaicism
- SOMETIMES the mother has REDUCED PENETRANCE or VARIABLE EXPRESSION i.e. disease is there but not expressed clearly.

Question 41

what is autosomal recessive inheritance

Answer 41

mendelian
disease which is manifest in the homozygous state
Male and females affected in equal proportions.
Affected individuals only in a single generation. Parents can be related e.g consanguineous

Question 42

example of autosomal recessive condition

Answer 42

cystic fibrosis

Question 43

what is X linked recessive inheritance

Answer 43

caused by pathogenic variants in genes on the X chromosomes

Question 44

how are X linked disorders usually transmitted

Answer 44

through unaffected females

Question 45

can X linked be passed from father to son and why

Answer 45

X-linked can never be passed from father to son (NO MALE-TO-MALE TRANSMISSION - BECAUSE SONS ALWAYS GET THEIR X CHROMOSOME FROM THEIR MOTHER) - all sons from affected male and unaffected female are unaffected.
* All daughters from an affected male are CARRIERS all sons are UNAFFECTED
* Males can NEVER be carriers
usually only males are affected

Question 46

how many defective genes do you need for autosomal recessive

Answer 46

2

Question 47

define lyonisation

Answer 47

the process of X chromosome inactivation
One of the two X chromosomes in every cell in a female is randomly inactivated early in embryonic development

Question 48

example of x linked dominant disease

Answer 48

Alports syndrome (kidneys)

Question 49

exaple of x linked recessive disease

Answer 49

duchennes muscular dystrophy