genetics 3: Inheritance and populations Flashcards
what are the main classes of mutations?
eletions - gene, exon, nucleotide(s) Insertions Single base substitutions Missense (amino acid replacements) Nonsense (premature stop codon) splice site Frameshift Dynamic mutations
what are the two types of inheritance ?
medelian and X-linked.
how do autosomal recessive medelian disorders occur?
Caused by mutations that result in loss of functional gene product eg, insertions, deletions, premature stop codons, frame shift mutations.
what gene is deleted in CF patients?
phenylalanine 508 in rhe CFTR gene
what does severity of disease depend on?
Severity of disease depends on the type and site of the mutation
describe what phenylketonuria is ?
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
define consanguinity
when there an offspring is from parents who share a common ancestor.
what is the inbreeding coefficient
look at slides. Sibs 1/4 Half sibs 1/8 Uncle/niece 1/8 First cousins 1/16 Second cousins 1/32
what is genomic imprinting?
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.
give an example of genomic imprinting
For example, the gene encoding insulin-like growth factor 2 (IGF2/Igf2) is only expressed from the allele inherited from the father.
What type of mutation occurs in Prader-Willi Syndrome and Angelman Syndrome ?
Loss of function
Sx of prader-willi?
Prader-Willi syndrome (PWS): Phenotypes mental retardation Hypotonia gross obesity (diabetes) male hypogenitalism Cause (on Paternal chr 15) Deletion of genes in 15q11-13
Sx of Angelman syndrome?
Mental retardation Lack of speech Growth retardation Hyperactivity Inappropriate laughter Cause (on Maternal chr 15) Deletion in 15q11-13 region
how do mendelian disorders occur in terms of autsomal dominant?
often manifest in either gene products with novel functions or genes expressed in an unregulated fashion.
What type of mutation if HD?
Gain of function mutation
caused by repeated CAG in hungtintin gene.
what are the sx of HD?
Autosomal dominant Progressive neurodegenerative disease Strikes in mid (50s) or later life Dementia Severe depression Chorea (involuntary, dance-like movement)
what is the unstable CAG repeat number?
36 - >100
what is cafe au lait spots seen in
neurofibromatosis
what autosomal dominant disorder causes variable expression
neurofibromatosis
what is fragile X
A genetic syndrome that is the most widespread single-gene cause of autism and inherited cause of mental retardation among boys
how is lysonisation protective?
X-chromosome inactivation (Lyonization). Females can inherit disorder genotype, but not express condition – reduced penetrance.
give an example of a mitochondrial inherited disorde?
Leber hereditary optic neuropathy
give an example of a germline mosaic inherited disease
DMD
what are some types of genetic testing?
Prenatal screening
Newborn screening
Carrier screening
Diagnostic screening, presymptomatic diagnosis
define genetic test
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.
why are genetic tests carried out?
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.
how are genetic tests carried out?
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).
what type of test is a diagnostic genetic test?
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.
what is a carrier test used for?
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.
what is a predictive/asymptomatic genetic test used for?
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.
what is a whole exome test used for?
- 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.
what is a whole genome test used for?
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.
what are amiocentesis and CVS test used for?
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.
what are newborn blood spot screening test used for?
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.
