Lecture 5 - Monogenic Inheritance Flashcards
Monogenic
- one gene governs a particular trait
- discontinuous variation
- high penetrance
Polygenic
- many genes affect one trait
- continuous variation
- low penetrance
Monogenic Disorder
- disorder caused by defect in one gene
- inherited by Mendilian Inheritance
Multiple Allealism/Alleilic Heterogenity
- many different allelles on the same locus are capable of causing disease
- example: CF
Locus Heterogenity
- many different loci are capable producing the same disease
- example: Retinitis Pigmentosa
Genetic Hetereogenity
-single disease can be manifested by different genetic mechanisms/diff genes at diff loci
Pleiotrophy
-single gene capable of causing multiple traits
AD main features
- expressed in both Hetero + homozygotes
- on average -> half offspring affected (equally amongst men and women)
- paternal age ->correlated with freq of new mutation
- variable penetrance + expressivity
- vertical degree pattern
What does AD usually affect
- structural proteins
- carriers
- receptors
AD Diseases
1) Achondroplasia
2) Marfans
3) Osteogenesis Imperfecta
4) Familial Hypercholestremia
5) Huntington’s
Achondroplasia
-defect in FGFR-3
> normally has neg affect on bone growth –> makes it constinutively active
Marfan Syndrome
-FBN1 gene ->defect in Fibrillin 1 –>defective Microfibrils of ECM
-CT disorder affecting:
> Eye
> Skeletal
> CV
Familial Hypercholestremial
-defect in LDL-R –> high amount of LDL–> Xanthomas+ Arthemas
- Multiple Allelism/Allelic Heterogenity
- Locus Hetereogenity
Difference in Homo and Hetero in Familial Hypercholestremia
Homo -> die of MI at 30
Hetere -> Coronary A disease by 40
Osteogenesis Imperfecta
- mut in COLIA (produces Collagen 1)
- brittle bones + blue sclera + deafness
*PLEIOTROPHY -> variable expressivity
Huntington
- CAG repeat in huntington gene –> Glu residues –> caspase cleaves that shit –> toxic
- # of repeats = severity/onset
AR Main features
- only in Homo
- Freq + Severity equal in each sex
- Horizontal pedigree -> single generation is affect (parents no)
What does AR affect
-enzymes
Diseases that are AR
1) PKU
2) CF
3) CBAVD
4) AR Deafness
5) Xeroderma Pigmentosum
6) Albinism
7) Sickle Cell Anemia
8) Tay-Sachs
Albinism
- defect in Tyrosinase
- no tyrosine -> melanin
PKU
- defect in PAH
- PA is an essential AA
- no PAH -> excess PA + PA-ketones
Problems with PKU
Brain Damage: > inhibit NT synthesis > AA transport > lack of neuronal development > defective myelin synthesis
Decr Pigmentation
How to detect PKU
Guthrie Test
AR Deafness
- defect in Connexin 26 (GJB2)
- Connexin imp in K+ Hemostasis in the Cochlea of the Inner Ear
