Multifactorial disease Flashcards
What does polygenic mean?
the result of the action of multiple genes
What is familial clustering (Lamda S)
the relative risk to a person in a family where another sibling has the condition by comparison to the risk of the population
What are SNPs?
Single nucleotide polymorphisms - change in the letter code at one point
Alzheimer disease
most common form of dementia
familial clustering is lamda s 3 to 10
much of the effect is due to a gene implicated in heart disease: app-lipoprotein E (APOE)
Which disease is associated with apo-lipoprotein E?
Alzheimer’s disease
Which Apo-lipoprotein E haplotype increases susceptibility of alzheimers?
ApoE 4 increases susceptibility
Which ApoE haplotype has a protective effect of alzheimers?
ApoE2
Age-related macular degeneration
characterised by the early deposition of drusen, a risk factor for AMD
leading to cause of irreversible central vision dysfunction caused by degeneration of the macula
What disease is characterised by the early deposition of drusen?
Age-related macular degeneration
what are the genetic causes of age-related macular degeneration?
CFH, ARMS2
Environment effects of Age related macular degeneration
smoking
light exposure
what does penetrance mean?
proportion of individuals with a specific genotype who manifest that phenotype
What are gatekeepers?
gatekeepers directly regulate tumour growth, they monitor and control cell division and death, preventing accumulation of mutations
what are caretakers?
They improve genomic stability and repair mutations
what is the function of tumour suppressor genes?
To protect cells from becoming cancerous
What can loss of function of tumour suppressor genes lead to?
cancer
What are oncogenes?
Regulate growth and differentiation
gain of function may result in activating mutations and increase the risk of cancer
what type of genes obey the two hit hypothesis?
cancer genes
Retinoblastoma
childhood ocular cancer
both genes are mutated
inherited cases at younger age
bilateral cases almost always germline
Familial adenomatous polyposis
hundreds of bowel polyps from teens onwards
high risk of bowel cancer if untreated
APC tumour suppressor gene affected
Hereditary non-polyposis colorectal cancer (NHPCC)
polyps are common but not polyposis
risk of bowel adenoma or cancer
mismatch repair genes
which phase in the cell cycle are the chromosomes most visible?
Metaphase
Which type of genetic testing are metaphase chromosomes used?
G banding
what is diploidy?
2 copies of each chromosome
What is aneuploidy?
gain or loss of chromosome, trisomy or monosomy
where do chromosome numerical abnormalities originate?
gametogenesis - meiosis
increased risk of aneuploidy with increased maternal age
fertilisation - polyploidy
early cleavage - post zygotic non-disjunction
What are the main features of downs syndrome?
upward slanting and brush field spots in eyes small nose microcephaly single palmer crease sandal gap protruding tongue short neck males = infertile increased risk of cancer, alzheimers, obesity
what chromosome is affected in downs syndrome?
trisomy 21
What syndrome is trisomy 18
Edwards syndrome
what are the main features of Edwards syndrome?
microcephaly low set ears rocker bottom feet clenched hands cleft lip and palate severe mental retardation short sternum may umbilical/inguinal hernia, congenital heart disease
What syndrome is trisomy 13?
Patau syndrome
What are the main features of patau syndrome?
sloping forehead low set ears, abnormal cleft lip abnormal genital brain defects - holprosencephaly polydactyly and fingers flexed mental retardation
Turners syndrome 45 X
loss of ovarian function, no puberty webbed neck swelling of hands and feet short stature coarctation of aorta
Klinefelters syndroms 47XXY
infertility hypogonadism testicular dysgenesis gynacomastia accelerated growth long limbs
What is a molar pregnancy?
double paternal chromosomes
no maternal
If have double maternal chromosome what are the consequences?
small placenta
small foetus with macrocephaly
If have double paternal chromosome what are the consequences?
foetus is normal with facial abnormalities, huge overdeveloped cystic placenta, genome for placenta
Which direction are DNA sequences written in?
5 prime to 3 prime direction
What is the definition of a gene?
functional unit of DNA
components:
exons, introns, regulatory sequences
What is a pseudogene?
used to be a gene then mutated and became non-functional
what is a processed gene?
a copy of a gene which is normal looking but without introns
what is satellite DNA?
large blocks of repetitive DNA sequence
large blocks are centromeres and heterochromatic chromosomal regions
what is alphoid DNA
a type of DNA found at centromeres
171 bp repeat unit
alphoid DNA is required for assembly of the centromere
what disease is associated with deficiency of blood coagulation factor 8?
Haemophilia A
Haemophilia A mutaiton
x linked recessive
blood coagulation does not work due to deficiency of blood coagulation factor 8
