common diseases Flashcards
how ti assess genetic involvement in etiology
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
pedigree
1) simple diagram of a family genealogy
2) shows family members relationships to each other and how a trait has been inherited
pedigree symbols
1) memorize them
2) oldest child on the left
autosomal dominant
1) vertical pattern of passing the condition
autosomal recessive
1) affected ones have horizontal pattern
2) carriers are heterozygous
no AD pattern, no AR pattern but higher proportion of affected individuals among relatives
1) it means genetics are involved somehow
2) need to learn beyond single gene mutation
monogenic
1) autosomal dominant
2) autosomal recessive
3) x-linked recessive
polygenic
1) usually part of multifactorial etiology
2) many genes
3) multifactorial means polygenic + environmental factors
chromosomal aberrations
1) numerical
2) structural
human diseases are a spectrum
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
recurrency
1) genetic, unifactorial
- high recurrency
2) multifactorial
- lower recurrency
congenital malformation
1) cleft lip and palate
2) congenital dislocation of hip
3) heart defects
4) neural tube defects
5) pylorostenosis
6) talipes
genetic susceptibility
1) polygenic
- susceptibility / candidate genes
2) several gene variants are interacting or adding to form it
3) “genotype”
acquired susceptibility
1) may be prone to diseases that are combo of genetic and environmental factors
heretibility
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
heritability scale
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
continuous normal distribution people
1) ronald fisher
- father of modern stats
- ANOVA
- stats in genetics
2) falconer
- quantitative genetics
- calculation in population genetics
continuous normal distribution
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
discontinuous distribution
MFT - threshold model of liability
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
liability
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
population incidence vs familial incidence
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%
cleft lips and palate
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
birth prevalence of nonsyndromic clefts
1) 1/350 to 1/1000 in newborns
- 1/920 in california
etiology of cleft lip and palate
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
genetic factors (candidate or susceptibility gnes)
1) genes linked to folate metabolism
2) genes controlling growth
environmental factors
1) nutrition, lack of folate
2) lifestyle
3) candidate nutrients
highest risk of recurrence
1) subgroups with highest proportion of genetic factors
2) females with bilateral cleft high
3) siblings of males with unilateral low
methods to identify genes for multifactorial malformation and disorders
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
diabetes mellitus
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)
inflammatory bowel disease
1) crohn disease - 1% of population
2) ulcerative colitis 2% of population
3) 200 susceptible loci
coronary artery disease
1) 60 susceptible loci
schizophrenia
1) 0.2% of population
2) 100 associated loci
alzheimer disease
1) 20 associated loci
2) APOE - 2,3,4 most important risk factor
