Week 2 Flashcards
complex inherited disorder?
Something that has been inherited but is not following mendalians rules
polygenic disease?
A disease caused by a number of genes/alleles
multifactorial disease?
Disease caused by a number of factors including both enviromental and genetic
What is cluster headache?
very sharp headache that is usually only one one side of the brain and last for a few weeks
What is Lambdas s ?
The relative risk of someone inheriting a disease that is already in there family in relation to the general population?
Is the risk of inheriting a disease greater for the general population or a person whos sibling has the disease and why? Lambdas s
person who has a sibling because of genetic similarities with there sibling
Is blood pressure a mendalian inheritance?
No it is affected by a number of factors
Give examples of congenitial malformation
cleft lip/palate, congenital hip dislocation, congenital heart defects, neural tube defects, pyloric stenosis, talipes
What can the mother take to reduce the chance of neural tube defects?
Take folic acid before the preganancy too 3 months after conception –> reduce chance by 50% too 70%
Give examples of acquired disease of childhood and adult life
asthma, autism, cancer, diabetes mellitus, epilepsy, glaucoma, hypertension, inflammatory bowel disease (Crohn disease), ischaemic heart disease & stroke, bipolar disorder, multiple sclerosis, Parkinson disease, psoriasis, rheumatoid arthritis, schizophrenia
What is the genome wide assoication study?
when you get two groups of people one controlled and one test group. You try to make everything identical between the two groups such as age, ethnicity, gender except for one group has the disease. You then compare there genome for the cause of the disease
What is linkeage anaylsis used for?
mendalian inheritance
Does SNPs usually cause a disease?
No they are usually harmless
What is the common age too get AD?
Over 40
What are the common symptoms of AD?
Memory loss, brain damage and inability to cope
What is the cause of AD neurologically?
shrinkage of brain, tangles of b-amyloid protein in nerve fibres of hippocampus
what is the relative risk of second sibiling having AD ?
ls is 3 to 10
What is the genetic cause of early onset AD?
is caused by Genetic heterogeneity
Which polymorphism of apo-lipoprotein E has greatest cuase of onest of AD and which gives the best protection
APOE 4 while APOE 2 gives the biggest proteciton
Having the APOE4/E4 reduces the onset of AD to when
from 84 yrs old too 68
what is the leading causeirreversible central visual dysfunction?
AGe related macular degeneration
What are the two most common genetic and enviromental causes of age related macular degeneration ?
CFH (1q), ARMS2 (10q) and smoking, light (UV to the eye)
Examples of polygenic disease
schizophrenia, type II diabetes, Alzheimers and age-related macular dystrophy
Can one mutation cause cancer?
Usually no need a multiple of mutations to cause cancer unless you have already inherited mutated genes
What factors affect the pentrance of someone having cancer?
genetic variation and enviromental factors can affect the penetrance of a population
what does a gate keeper cell do?
Regulated tumur growth: monitors and controlls cell divison and death. Prevents mutation accumulation
name a gate keeper gene
TP53
what does caretakers do?
they improve genomic stability
landscape
control the surrounding stromal enviroment
what is the supporting cell that has the mutation in certain colonel cancers?
stromal cells surrounding the epithelial cells
what are the chances of developing colonal cancer if you have a mutation in a tumor suppresant gene (gate keeper)?
95%
What are the hances of developing colonal cancer if you have a sporadic mutation?
look at powerpoint
give examples of tumor suppressor genes
e.g. APC, BRCA1/2, TP53, Rb
BRCA1/2 –> cause of breast cancer
what does oncogenes do?
regulate cell growth and differentation
how does mutation in oncogenes cause mutation?
causes a gain in function and activation
give example of oncogenes mutation?
mutation in the RET gene that cause multiple endocrine neoplasia
who hypothesised the two hit theory for cancer?
Knudsons
how many alleles need to be knocked down in sporadic cancer?
two
How many alleles need to be knocekd down in inherited cancer?
1–> increase the likely hood of having cancer
Is inherited cancer dominant or recessive at cellular level?
It is recessive. You need both alleles to develop the cancer
Is the inherited pathway ( family tree) usually AD or Recessive in terms of inherited cancer?
Autosomal dominant because the inheritance is sporadic in the second knock down
give example of cancers that are passed down in autosomal recessive pattern
MYH associated polyposis, Fanconi anaemia, Ataxia telangiectasia
HOw does autosomal recessive pattern of inheriting cancer work?
Each of the parents have one copy of the gene and are usually not affected. There is 25% chance the child could be affected
What is misense mutation?
Misense mutation is when there is a change in base and causes the formation of a different amino acid and can affect what protein is produced
what is nonsense mutation?
A point mutation causes the change of one base –> cause the protein strand to be cut short
how to find familiar cancer gene
family studies –> linkage analysis
candiate gene analysis
whole exome sequencing
what facotrs you need for to take a family history
paternal and maternal side
3 generations
confirmation –> cause of death, date, death certificate, medical records
type of cancer, age of diagnosis
Does sporadic cancer usually occur in elderly people or in young people? define the age limit
Elderly people >50
In sporadic cancer inheritance is it common for number of family members to have the cancer?
No it is not passed on
What factors make familial cnacer?
usually occur before 50, more than 1 member of the family has familar cancer type, occurs in both young and old
in children what type of cancer is most common?
hematological and brain tumors.
what is diagnostic genetic testing?
genetic testing is done on someone who has cancer and we are identifying the gene that causes it on their DNA
Predictive genetic testing
Is to determine if someone has the mutation that makes them prone to having a cancer that is already present by a family member
what is Retinoblastoma?
childhood occular cancer
what is Familial Adenomatous Polyposis FAP?
thousands of polyps in the colon
what is the risk of having bowl cancer if you have FAP and leave it untreated?
up to 100%
what mutation causes FAP?
mutation in the APC tumor suppressor gene
what type of inheritance is Familial adenomatous poylposis?
Autosomal dominantly inherited
what is the surgical procedure if you have FAP?
Prophylactic colectomy –>you need to cut the part of the colon that has the polyps and then attatch the rest of it to the rectum
what is Hereditary Non-Polyposis Colorectal Cancer NHPcc?
Development of a few polyps not the same as FAP that can lead to bowel cancer –> most common cause 2-3%
Can also lead to other types of cancer such as ovarien endometrial/ovarian/stomach/GU
What type of inheritance is NHPcc
Autosomal dominant inheritance
What is the amsterdam criteria for NHPcc
One member diagnosed with colorectal cancer before age 50 years
Two affected generations
Three affected relatives, one of them a first-degree relative of the other two
FAP should be excluded by histological report
Tumours should be verified by pathologic examination
how often should patients wiht NHPcc have colonoscopy for screening and from what age?
every 18-24 months and from age 25
What do BRCA1/2 do?
they are invovled in DNA repair
In what community is it common to have the BRCA1/2 mutation?
jewish community
What is the risk of having breast cancer with BRCA1/2 mutation?
80%
What are the chances of getting ovarian cancer if you have either BRCA1/2 mutation?
40% for BRCA1
10 for BRCA2
What other cancers are more common if you have BRCA1/2 mutation?
male breast cancer, melonoma and prostate cancer
Option of reducing the chance of having breast cancer?
mastectomies
what mutation causes Li Fraumeni Syndrome?
P53 and rare
Is Li Fraumeni Syndrome AD or AR?
autosomal dominant
what is the risk of developing cancer if you have Li Fraumeni Syndrome?
50% by 40 and 100% in your lifetime
What type of treatment should you not use if you have Li–Fraumeni syndrome is a rare cancer predisposition hereditary disorder characterized as autosomal dominant.?
Should not use radiotherapy as it can induce the cancer
Why is there no point in doing screening for Li–Fraumeni syndrome is a rare cancer predisposition hereditary disorder characterized as autosomal dominant.?
if you are positive there is nothing you can do
What is the average onset of Li–Fraumeni syndrome ?
during childhood
what is Li–Fraumeni syndrome?
rare cancer predisposition hereditary disorder
what type of curve does normally distributed traits follow
Gaussian “bell-shaped curve
