common diseases

Question 1

how ti assess genetic involvement in etiology

Answer 1

1) family history (pedigree)
- if positive, genetics in etiology likely
2) medical history
- can point environmental factors - trauma, tumor, habits
3) correct diagnosis
- sources and information in the literature
4) previous treatment outcomes

Question 2

pedigree

Answer 2

1) simple diagram of a family genealogy
2) shows family members relationships to each other and how a trait has been inherited

Question 3

pedigree symbols

Answer 3

1) memorize them
2) oldest child on the left

Question 4

autosomal dominant

Answer 4

1) vertical pattern of passing the condition

Question 5

autosomal recessive

Answer 5

1) affected ones have horizontal pattern
2) carriers are heterozygous

Question 6

no AD pattern, no AR pattern but higher proportion of affected individuals among relatives

Answer 6

1) it means genetics are involved somehow
2) need to learn beyond single gene mutation

Question 7

monogenic

Answer 7

1) autosomal dominant
2) autosomal recessive
3) x-linked recessive

Question 8

polygenic

Answer 8

1) usually part of multifactorial etiology
2) many genes
3) multifactorial means polygenic + environmental factors

Question 9

chromosomal aberrations

Answer 9

1) numerical
2) structural

Question 10

human diseases are a spectrum

Answer 10

1) genetics to environmental
2) congenital
- muscular dystrophy
- osteogenesis imperfecta, etc
3) environmental
-scurvy
- TB
4) both
- cleft lip/palate
- congenital dislocation of the hip
- congenital heart defects
- neural tube defect
- pyloric stenosis
- asthma
- diabetes
- glaucoma
- hypertension
- IBD
- parkinsons
- psoriasis
- rheumatoid
-etc

Question 11

recurrency

Answer 11

1) genetic, unifactorial
- high recurrency
2) multifactorial
- lower recurrency

Question 12

congenital malformation

Answer 12

1) cleft lip and palate
2) congenital dislocation of hip
3) heart defects
4) neural tube defects
5) pylorostenosis
6) talipes

Question 13

genetic susceptibility

Answer 13

1) polygenic
- susceptibility / candidate genes
2) several gene variants are interacting or adding to form it
3) “genotype”

Question 14

acquired susceptibility

Answer 14

1) may be prone to diseases that are combo of genetic and environmental factors

Question 15

heretibility

Answer 15

1) mathematical estimate of proportion of genetic and environmental factors in etiology of a specific trait or disease or malformation
2) proportion of affected and unaffected individuals in a group of relatives
3) population incidence of specific trait diseases or malformation
4) best studied in DZ and MZ twins

Question 16

heritability scale

Answer 16

1) 0.5
- same proportion of G and E
2) 0.8
- stronger genetic influence
- ex. mandibular prognathism
3) 0.3
- small genetic influence
- open bite / over but due to thumb sucking

Question 17

continuous normal distribution people

Answer 17

1) ronald fisher
- father of modern stats
- ANOVA
- stats in genetics
2) falconer
- quantitative genetics
- calculation in population genetics

Question 18

continuous normal distribution

Answer 18

1) height
- 1,2,3 loci
- combination of 697 common variants (20% heritability)
2) intelligence
- IQ scores follow normal std
3) skin color
- three sets of alleles which form pigmentation
- bell curve
4) hair color
5) eye color
6) BP
7) dermatoglyphics
8) head circumference
9) BMI

Question 19

discontinuous distribution

Question 20

MFT - threshold model of liability

Answer 20

1) sewell green wright
- studies based on evolutionary theory and population genetics
2) clark fraser
- discipline of medical genetics
- studied human diseases
- established genetic counsels
- liability

Question 21

liability

Answer 21

1) describe all the genetic and environmental factors that contribute to a multifactorial disorder
2) a threshold that is reached will lead to every individual affected

Question 22

population incidence vs familial incidence

Answer 22

1) first degree relatives is approx the square root of the population incidence
- shifted to the right
2) if the incidence is 1/1000 for recurrence, in 1st degree relatives (siblings and offspring) will be 1/32 or 3%

Question 23

cleft lips and palate

Answer 23

1) multifactorial etiology
2) 1/566 newborns in US
- cleft lip with or without palate or cleft palae only
3) everyday in USA, 14 babies with CL/P and 7 babies with CP are born

Question 24

birth prevalence of nonsyndromic clefts

Answer 24

1) 1/350 to 1/1000 in newborns
- 1/920 in california

Question 25

etiology of cleft lip and palate

Answer 25

1) environmental
- FAS, embryopathy, multicongenital anomalies
- teratogens, isolated cases
2) combination
- cleft lips without other anomalies
3) mostly genetics
- syndromes, chromosomal aberrations
- down syn, treacher collins syn,

range from environmental to genetic
males with uni, females with uni, males with bilateral, females with bilateral

Question 26

genetic factors (candidate or susceptibility gnes)

Answer 26

1) genes linked to folate metabolism
2) genes controlling growth

Question 27

environmental factors

Answer 27

1) nutrition, lack of folate
2) lifestyle
3) candidate nutrients

Question 28

highest risk of recurrence

Answer 28

1) subgroups with highest proportion of genetic factors
2) females with bilateral cleft high
3) siblings of males with unilateral low

Question 29

methods to identify genes for multifactorial malformation and disorders

Answer 29

1) association studies - case control studies
2) microarray
- genotyping hundreds of thousands of SNPs
3) haplotype map
- reference catalogs of SNPs and linage disequilibrium
4) GWAS
5) imputation
6) reference panels

Question 30

diabetes mellitus

Answer 30

1) type 1 - 0.4% of population with 50 distinct genomic loci
2) type 2 - 10% of population
- 90 susceptible loci (no overlap with type 1)

Question 31

inflammatory bowel disease

Answer 31

1) crohn disease - 1% of population
2) ulcerative colitis 2% of population
3) 200 susceptible loci

Question 32

coronary artery disease

Answer 32

1) 60 susceptible loci

Question 33

schizophrenia

Answer 33

1) 0.2% of population
2) 100 associated loci

Question 34

alzheimer disease

Answer 34

1) 20 associated loci
2) APOE - 2,3,4 most important risk factor