Genetics Flashcards
How common are genetic diseases?
4-5% of all live births
30% of admissions to paediatric wards - congenital abnormalities
10% adults have disease with genetic component
5% common cancers such as breast and colon cancer due to underlying genetic predisposition
What is the role of a clinical geneticist?
Involved in making diagnoses
Explain diagnosis to family
Discuss prognosis
Discuss options available - genetic testing, screening, prenatal diagnosis
Refer to appropriate specialist for management
Help people understand and adapt to medical, psychological, and familial implications of how genetic contributes to disease
Guide individuals/families in discussions about test result interpretation, prevention, medial management, and options for prenatal diagnosis
Not involved in diagnosis
What referrals do clinical geneticists get?
Preconceptual - genetic testing Antenatal - scans/tests Paediatrics - not meeting milestones ect Carrier testing Adult onset conditions Post mortem
What are the categories of genetic disorders?
Single gene disorders - mendelian inheritance
Chromosomal disorder - affects thousands of genes so multiple organ systems affected
Multifactorial - several genes acting with environmental influences, usually only affects one organ system
Spectrum of conditions
Name 3 types of genetic disease
Down’s syndrome
CF
Huntington’s disease
Haemophilia
Name 3 types of multifactorial disease
Spina bifida
Cleft lip/palate
Diabetes
Schizophrenia
Name 3 types of environmental disease
Poor diet
Infection
Accidents
Drugs
What are the different types of single gene disorders?
Autosomal dominant
Autosomal recessive
X-linked
What can cause chromosomal abnormalities?
Changes in number/structure
Entire chromosomes/individual chromosomes/alterations within individual chromosomes
What is polyploidy?
Increase in number
What is it called where you lose a chromosome?
Monsomy
What is it called where you gain a chromosome?
Trisomy
What is euploidy?
Normal number of chromosomes
What is aneuploidy?
Abnormal number of chromosomes
What is a common cause of aneuploidy?
Non-disjunction
Failure of chromosomes to separate at anaphase
Can occur in meiosis 1/2
Name 2 causes of chromosomal conditions
Unbalanced translocation
Non-disjunction
What should you do if a baby has chromosome translocation?
Test the parents
How common in aneuploidy?
35-70% of early embryonic deaths and spontaneous abortions caused by aneuploidy
1 in 170 live births
What are the possible clinical effects of cytogenetic abnormalities?
Congenital abnormalities
Delayed development - usually severe
Dysmorphic features
Small stature, microcephaly, failure to thrive
In adults - infertility, stillbirths, miscarriages
How might autosomal dominant inheritance present in a family?
Each child has 50% chance of inheriting mutation
Equally transmitted by men and women
Often affected individuals in multiple generations
Vertical transmission
Mutation transmitted from male to male
Sex can be limited
Only one copy of gene pair altered
May have variable penetrance and often variable expression
Possibility of new mutations
Gonadal mosaicism may occur
Name 3 causes of autosomal dominant inherited conditions
Adult PKD Familial hypercholesterolaemia Marfan's Huntington's disease Familial breast and ovarian cancer
What is gonadal mosaicism?
Condition in which the precursor cells to ova and spermatozoa are a mixture of 2 or more genetically different cell lines
What is autosomal recessive inheritance?
2 germline mutations to develop disease
How might autosomal recessive conditions present in families?
Equally transmitted by men and women
Unless consanguinity usually only one generation affected
Both parents heterozygous carriers
1 in 4 recurrence risk for siblings
2 in 3 carrier risk for unaffected siblings
Usually low risk for children of affected person or half-siblings - depends on population carrier frequency
Increased risk in consanguineous families
