Genetics of Common Hereditary Diseases (A), B Flashcards
both genetics and environmental are involved
hypertension, cerebrovascular, CVS disorders, schizophrenia.,
DM
Features of Multifactorial Diseases:
• Most affected children have normal parents.
• Recurrence risk increases with the number of affected children in a family.
• Recurrence risk increases with severity of defect. A more severely affected parent is more likely to produce an affected offspring.
• Most isolated congenital anomalies are multifactorial inheritance.
- consanguinity slightly increased the risk for an affected child.
Neural tube defects is multifactorial inheritance determined by multile genetic and environmental factors
However, the impact of folic acid deficiency is Along with folate deficiency , there is elevated homocysteine level in blood with defective/recycling of homocysteiné to methionine.
exacerbated by a genetic mutation in MTHER (methylene tetrahydrofolate reductase).
• Non-Mendelian inheritance:
• Mitochondrial inheritance.
• Mosaicism
- Germline or gonadal.
- Somatic.
Multifactorial and polygenic:
- Congenital: - present at birth.
- Common diseases: - becomes evident
sometimes after birth as diabetes mellitus
• Several genes each on its own does not cause any problems but the aggregate of genes acting with some environmental factors lead to the disease or trait called
(multifactorial means polygenic inheritance plus
environmental factors).
• We say two related individuals are ………….. for a disorder if they have the same disease.
• When only one member of a pair has the disorder we say they are
concordant
discordant.
• Example of Multifactorial Diseases:
•Neural tube defect.
•Cleft lip and palate.
•Club foot.
•Pyloric stenosis.
•Congenital heart defects.
•Congenital dislocation of the hip.
•Hypertension.
• Atherosclerosis.
•Diabetes mellitus.
Cardiac Anomalies
Trisomy 18
Trisomy 21
Marfan Syndrome
Marfan Syndrome: Aortic root dilatation &
dissection, MVP (multiple valve prolapse)
Associated Genes: FBN1, TGFBR1, TGFBR2
Trisomy 18 : ASD, VSD, PDA, TOP,DORV, COA, BAV
90-100%
Trisomy 21 ASD, VSD, AVSD, TOE 40-50%
Tetralogy of Fallot > 4 defects;
• TOF: Tetralogy of Fallot -> 4 defects; VSD,pulmonary stenosis, a misplaced aorta and right ventricular hypertrophy leading to lack of 02-rich blood reaching the body.
• Vascular endothelial growth factor (VEGF) plays a critical role in the ……………… during heart development in mouse model.
formation of the endocardial cushions
• Three single nucleotide polymorphisms (SNPs) in the promoter of VEGF (C2578A, G1154A and C634G) shown to be a modifier of ……. deletion syndrome. Same haplotype was associated with dower VEGF
level in vivo.
• In family based study, the low expression of VEGF haplotype was transmitted more often to affect children suggesting that it may play a role in the development of isolated……
22q11
TOF
• Newer data: VEGF do not play significant role in CHD.
Causes of Autoimmunity
Environmental Factors:
• lodine
•Selenium
•Drugs
•Infections
•Stress
•Pollution/Toxins
•Gluten
•Overly sterile
environment
Genetic Factors: •HLA-DR
•HLA-DQ2 & DQ8.
• CTLA -4
Endogenous Factors:
• High(leptin)levels
• Vitamin Deficiencies
•Gut micro-floral balance
• Leaky gut
• Pregnancy
pal pale grove
•Menopause
•Rapid Growth
• Puberty
•Aging
• Female Sex
•Emotional Vulnerability
Examples of Autoimmune Diseases:
•Type DM.
@Multiple Sclerosis.
@Rheumatoid Arthritis.
E Graves Disease.
• Systemic Lupus Erythrematosus.
Rheumatoid Arthritis:
Symptoms:
-Joint pain, swollen joints.
• Small joints are affected.
It affects lungs, blood vessel , heart, kidneys, eyes, skin & nerve tissue.
*Bone marrow ->
Anemia.
12
Rheumatoid Arthritis:
Diagnosis, Treatment:
-Physical examination.
- Blood tests: increased ESR, , increased CRP due to inflammatory process.
Rheumatoid factor & anti-cyclic citrullinated peptide (anti-CCP) ántibodies.
- Imaging tests: X-ray,MRI, US
Treatment:
1. Medications: NSAIDs, Steroids.
• Disease modifying anti-rheumatic drugs(DMARDs) ….etc.
2. Surgery: for severe cases.
