genetics 3: Inheritance and populations

Question 1

what are the main classes of mutations?

Answer 1

eletions - gene, exon, nucleotide(s)
Insertions
Single base substitutions
Missense (amino acid replacements)
Nonsense (premature stop codon)
splice site
Frameshift
Dynamic mutations

Question 2

what are the two types of inheritance ?

Answer 2

medelian and X-linked.

Question 3

how do autosomal recessive medelian disorders occur?

Answer 3

Caused by mutations that result in loss of functional gene product eg, insertions, deletions, premature stop codons, frame shift mutations.

Question 4

what gene is deleted in CF patients?

Answer 4

phenylalanine 508 in rhe CFTR gene

Question 5

what does severity of disease depend on?

Answer 5

Severity of disease depends on the type and site of the mutation

Question 6

describe what phenylketonuria is ?

Answer 6

Sever learning difficulties, fair skin, eczema, epilepsy
Caused by mutations in phenylalanine hydroxylase (PAH)
Autosomal recessive, chromosome 12q22-24.1
phenylalanine cant be coverted to tyrosine

Question 7

define consanguinity

Answer 7

when there an offspring is from parents who share a common ancestor.

Question 8

what is the inbreeding coefficient

Answer 8

look at slides. 
Sibs					1/4
Half sibs				1/8	
Uncle/niece				1/8
First cousins				1/16
Second cousins			1/32

Question 9

what is genomic imprinting?

Answer 9

An epigenetic modification of the genome in which some genes in the allele from one of the parents are closed down (methylated)
Imprinting is contorlled at the Imprinting Centre located nearby the imprinted areas on the same chromosome.

Question 10

give an example of genomic imprinting

Answer 10

For example, the gene encoding insulin-like growth factor 2 (IGF2/Igf2) is only expressed from the allele inherited from the father.

Question 11

What type of mutation occurs in Prader-Willi Syndrome and Angelman Syndrome ?

Answer 11

Loss of function

Question 12

Sx of prader-willi?

Answer 12

Prader-Willi syndrome (PWS):
Phenotypes
mental retardation
Hypotonia
gross obesity (diabetes)
male hypogenitalism
Cause (on Paternal chr 15)
Deletion of genes in 15q11-13

Question 13

Sx of Angelman syndrome?

Answer 13

Mental retardation
Lack of speech
Growth retardation
Hyperactivity
Inappropriate laughter
Cause (on Maternal chr 15)
Deletion in 15q11-13 region

Question 14

how do mendelian disorders occur in terms of autsomal dominant?

Answer 14

often manifest in either gene products with novel functions or genes expressed in an unregulated fashion.

Question 15

What type of mutation if HD?

Answer 15

Gain of function mutation

caused by repeated CAG in hungtintin gene.

Question 16

what are the sx of HD?

Answer 16

Autosomal dominant
Progressive neurodegenerative disease
Strikes in mid (50s) or later life 
Dementia
Severe depression
Chorea (involuntary, dance-like movement)

Question 17

what is the unstable CAG repeat number?

Answer 17

36 - >100

Question 18

what is cafe au lait spots seen in

Answer 18

neurofibromatosis

Question 19

what autosomal dominant disorder causes variable expression

Answer 19

neurofibromatosis

Question 20

what is fragile X

Answer 20

A genetic syndrome that is the most widespread single-gene cause of autism and inherited cause of mental retardation among boys

Question 21

how is lysonisation protective?

Answer 21

X-chromosome inactivation (Lyonization). Females can inherit disorder genotype, but not express condition – reduced penetrance.

Question 22

give an example of a mitochondrial inherited disorde?

Answer 22

Leber hereditary optic neuropathy

Question 23

give an example of a germline mosaic inherited disease

Answer 23

DMD

Question 24

what are some types of genetic testing?

Answer 24

Prenatal screening
Newborn screening
Carrier screening
Diagnostic screening, presymptomatic diagnosis

Question 25

define genetic test

Answer 25

A genetic test is a medical test, most often carried out on a blood sample, that looks for changes in a person’s genetic make-up.

Question 26

why are genetic tests carried out?

Answer 26

To help diagnose a suspected genetic condition. - To identify the specific underlying genetic change causing a genetic condition. - To help determine the chance of developing a genetic condition in the future. - To determine whether someone is a carrier of a genetic condition. - To clarify the chance of passing a genetic condition on to children. - To find out whether a developing baby or embryo has a particular genetic condition.

Question 27

how are genetic tests carried out?

Answer 27

blood sample from the patient’s arm. The genetic material is extracted from blood cells in the laboratory and used in the testing process.  saliva samples and skin biopsies.  Certain genetic tests can be carried out on a pregnancy by taking a sample of amniotic fluid from around the developing baby (in a procedure called amniocentesis), or a piece of material from the placenta (by a procedure called chorionic villus sampling).

Question 28

what type of test is a diagnostic genetic test?

Answer 28

Identify or exclude specific genetic conditions in an individual who has symptoms or signs of a genetic condition.  This type of test is most often used to confirm a diagnosis when a condition is suspected. 

Question 29

what is a carrier test used for?

Answer 29

see whether a healthy unaffected individual is a carrier of a genetic condition.  carriers of a genetic condition do not generally have any associated health problems themselves but there may be implications for children.  this type of test is usually offered to individuals with a family history of certain genetic conditions and to people in certain ethnic groups where there is an increased risk of specific genetic conditions. 

Question 30

what is a predictive/asymptomatic genetic test used for?

Answer 30

for someone who has a family history of a serious later onset genetic condition, for example Huntington’s disease, where the symptoms usually start sometime in adulthood. generally only offered to adults (18 years+) as the health implications are only in adulthood and there is a need to respect individual autonomy. 

Question 31

what is a whole exome test used for?

Answer 31

- a new type of genetic testing when doctors don’t know where in a person’s genetic make-up to look for the cause of the condition.  Instead of doing a targeted test for a particular genetic change or gene, whole exome testing looks at all genes in one test to search for the genetic change causing the disorder. 

Question 32

what is a whole genome test used for?

Answer 32

a new type of genetic testing being used in projects such as the 100,000 Genomes Project. It could, in the future, be used when doctors don’t know where in a person’s genetic make-up to look for the cause of their condition. 

Question 33

what are amiocentesis and CVS test used for?

Answer 33

diagnostic tests carried out on a pregnancy to look for a genetic condition affecting the developing baby. They are offered when there is an increased risk that the baby could have a serious genetic disorder.  The majority of prenatal tests for specific genetic disorders require the genetic cause of the condition in the family to have already been identified. 

Question 34

what are newborn blood spot screening test used for?

Answer 34

A small blood sample taken from the baby’s heel when they are about 5 days old.  The aim is to identify those babies with a serious treatable health problem so that treatment can be started as early as possible, and may reduce the severity of the condition.  The results generally take a couple of months to come back.