GENETIC FINAL

cancer

define = uncontrolled division of abnormal cells

apoptosis = PCD

maintain homeostasis

when damaged beyond repair, virus, stress, DNA damage 

loss of apoptotic control can lead to cancer

apoptosis morphology 

• discontinuous nuclear envelope
• condensation/shrink
• blebbing 
• DNA fragmentation = karyorrhexis
• apoptotic bodies - phagocytosis

necrosis 

• swelling
• smooth plasma membrane 
• disintegration/membrane rupture
• cell lysis 

cancer major changes 

• immortalization
• transformation/proliferation
• angiogenesis 
• metastasis 
• evasion of apoptosis 
• genetic instability 

influential factors

• environment
• reproductive life 
• lifestyle
• virus
• mutagenic 
• defect in DNA replication

hallmarks

• evading growth suppressor
• avoiding immune destruction
• enabling replicative immortality 
• tumor promoting inflammation
• activating invasion & metastasis 
• inducing angiogenesis 
• genome instability & mutation
• resisting cell death
• deregulating cellular energetics
• sustaining proliferative signaling 

normal cells

• need external signals 
• respond to inhibitory signals
• undergo apoptosis 
• shorten telomere
• depend on blood vessel
• no metastasis 
• cannot grow in low serum
• flat & extend
• anchorage dependence
• exhibit contact inhibition 

cancer cells

• angiogenesis 
• round
• anchorage dependence
• fail to exhibit contact inhibition 

oncogene dominant gain of fx 

proto oncogene (normal gene) 

tumor suppressor gene recessive loss of fx

Knudson's: 2 recessive = carcinogenesis = recessive mutation

haploinsufficiency = 1 allele mutated = express cancer phenotype

metabolism 

inborn errors of met AR or XR

carb:

PKD - PKLR 1q22

G6PD - XR

lactose intolerance - lactase, LCT

aa:

alkaptonuria - AR, homogentisate oxidase, HGD 

PKU - phenylalanine hydroxylase, PAH

albinism - tyrosinase, no melanin, TYR/HPS/CH

maple syrup urine - AR, DBT 

lipid:

Gaucher - glucocerebrosidase

Tay sac - beta hexosaminidase A

familial hypercholesterolemia - LDLR

urea:

hyperammonemia + arginase, argininosuccinate synthetase/lyase 

congenital - 

Type 1 - AR, carbamoyl phosphate synthetase 

Type 2 - XR, ornithine transcarbamoylase

Type 3 - AR

N acetyl glutamate synthetase deficiency - low CPS 1

acquired

SAQ

Dr suhaili

1. many genetic ds disabling/fatal still common, will recessive allele which is lethal in homozygous condition completely removed from a large population? elaborate factor involved with ds example

no 

presence of carrier 

achromatopsia 

Aa x Aa (AA is lethal) 

50% carrier

pass genes to offspring

2. relationship between ... that are able to change allele fx of a genetic ds 3%

bottleneck effect = drastic reduction in population - reduce diversity - 天灾

founder effect = small group isolated from main population - reduce diversity - migration

genetic drift = change in allele frequency from gen to gen due to chance 

natural selection = higher fitness higher survival

non random mating = choose partners based on specific traits 

3. how are chromosome ds been diagnosed 2%

karyotyping, fluorescence in situ hybridization FISH

4. 2 approach looking at susceptible gene for complex ds 4% - strategies for cloning a ds gene

functional cloning - when know biochemical basis of ds - gene encode for enzyme/protein that deficient in disease 

candidate gene - when able to guess what gene might be and test it directly in patients 

positional cloning - when know disease gene's location in genome 

5. write fully interpret reports for following 8%

a. 45, X/46, XX female recurrent miscarriage history

Turner syndrome with 45, X/46, XX mosaicism

b. 46, XX, del (14) (q23)

female with 46 chromosome with deletion on chromosome 14 long arm of region 2 band 3

c. 46, XY, dup (14) (q22q25)

male with 46 chromosome with duplication on chromosome 14 long arm of region 2 band 2 and region 2 band 5

d. 46, XX, r (7) (p22q36)

female with 7 ring chromosome

the end of p arm of region 2 band 2 fuse with the end of q arm of region 3 band 6

6. allele frequency 

p + q = 1

genotype frequency 

p2 + 2pq + q2 = 1

f (WW)=p2=6/9=0.67

f (Ww)=2pq=1/9=0.11

f (ww)=q2=2/9=0.22

f (W)=p= (2(WW) + Ww)/2 (9) = 0.72

f (w)=q=0.28

Lod score 

non recombinant: 8

recombinant: 2

recombinant factor = 2/10 = 0.2 = Θ

Z=0.837 = not linked 

Z more than 3 = linked

Z less than -2 = not linked 

Z = -2 ~ 3 need more data 

genetic mapping - suhaili

3 types of map

• cytogenetic
• linkage
• physical

5 molecular markers

• restrictive fragments length polymorphism = southern blot 
• amplified fragment length polymorphism = PCR technique
• minisatellites & microsatellites = STR/SSR & VNTR
• single nucleotide polymorphism = missense 
• sequence tagged site 

map molecular markers with linkage mapping & LOD mapping 

human development

1 pre embryonic period 2w

2 embryonic period 3-8w

3 fetal period 9- ~37w

regional specification: different pattern from initial similar cell population - form several region 

- gastrulation, neurulation, axis specification 

growth: complex interplay of hormone, nutrient, genes

morphogenesis: change in cellular shape 

cell differentiation: stem cell differentiate to differ fx 

 vs cell determination?

• gene
• signaling molecules
• CAM
• ECM
• cytoskeleton

holoprosencephaly: SHH, signaling molecules, growth - regional specification 

achondroplasia/hypo, thanatophoric dysplasia : FGFR, signaling molecules, growth or morphogenesis 

Duchenne muscular dystrophy: DMD, growth or morphogenesis

Alzheimer's/HTT, neuroblastoma, colon & small cell lung carcinoma: REST, zinc finger gene, differentiation

synpolydactyly: HOXD13, homeobox gene, morphogenesis

hand foot genital syndrome: HOXA13, homeobox gene

male sexual reversal (XY female): SOX9, HMG gene

define morphogen: 2%

substance that governs pattern of tissue development in morphogenesis 

sonic hedgehog SHH

fibroblast growth factor FGF

Dr deming

factors contribute: 4%

lifestyle - nutrients switch on or off certain gene expression - obesity - healthy diet silent lipogenic gene

habits - smoking - damage DNA, promote tumor growth 

socio economic 

geographic location

define heritability: 6%

proportion of observed variability in a trait within a population attribute from genetic differences among these individuals 

genetic contribution to multifactorial trait 

how to study:

low (0.0) = environment factor

high (1.0) = genetic play role in trait 

single gene ds

• clear family history
• early onset
• rare
• high accuracy for predict risk
• all cells 
• germline mutation - embryonic stage
• cystic fibrosis 

multifactorial ds

• long exposure to environmental factors 
• common
• specific cells 
• somatic cell mutation
• cancer

bioethics 2 question 

values: 

autonomy - patient has rights to refuse treatment

beneficence - practitioner should act in best interest of patient

non maleficence - "first, do no harm"

justice - for resource distribution, decision

dignity - way of treating patient & practitioner

truthfulness & honesty - informed consent required

why genetic interesting:

identify risk that not yet affect patient

about families as well as individuals 

genetic research is commercially driven to a substantial degree

issue of genetic testing: 

risk of being tested - psychological - bad gene positive: genetic determinism = possible overestimate of likelihood will suffer/become afflicted; negative: survivor guilt - overconfident no disease

public conceptions of genetics - beliefs - genetic determinism = idea of particular gene = particular trait 

confidentiality & consent & duty to warn 

commodifying genes - for commercialization - Myriad genetics holds patent on BRCA1&2 - insist only they can perform test for BRCA mutation