Intro to Medical Genetics Flashcards Preview

MS 1 Unit 7 MCP > Intro to Medical Genetics > Flashcards

Flashcards in Intro to Medical Genetics Deck (31):


-the study of hereditary


Human Genetics

-the study of heredity in man


Medical Genetics

-the study of human genetic variation of medical significance


Subunits of Medical Genetics

-Clinical Genetics- diagnosis
-Genetic Counseling- information
-Molecular genetics- lab
-Biochemical Genetics- lab
-Cytogenetics- lab



-a permanent, heritable change in the sequence of genomic DNA
-can occur at either the molecular or cytogenetic level
-may give rise to new alleles
-important mechanism of population variation
Neutral- blue eyes
Positive- sickle cell trait
Negative- sickle cell disease, cancer


Patterns of Inheritance

-dominant vs recessive
-autosomal vs X linked


Inherited gene complement

-mutations may be transmitted from one or both parents
-typically called the constitutional genome


Acquired gene complement

-a subset of cells in an individual that arose by clonal propagation from a single mutation in one cell



-set of characteristics which occur together and are assumed to have a common basis
-not all characters occur in all affected individuals
-range of variability within a population
-for example there are over 250 known features of the disorder velocardiofacial syndrome but no single individual has all of these findings
-however, for diagnosis to be made,an individual diagnosed with a particular disorder must have a core group of the cardinal characters associated with that disease


Biochemical Genetics

-subspeciality of genetics that deals with the diagnosis, treatment and research of inborn errors of metabolism


Inborn Errors of Metabolism

-genetically determined biochemical disorder in which a specific enzyme defect produces a metabolic block
-accumulation of substrate
-deficiency of products
-single enzyme defect
-many recognized disorders
-challenge to detect the particular substance and pathway involved
-alcaptonuria, cystonuria, pentosuria, albinism



-inborn errors of metabolism
-accumulation of homogentisic acid in the blood
-damage to cartilage, heart, kidney


Tyrosine to melanin

-Tyrosine to pigment A uses tyrosine oxidase
- if all functions correctly tyrosine will be converted to melanin which phenotypically presents as black or dark brown pigment
-if the pathway is blocked at enzyme X, the conversion is incomplete and only some pigment will be present resulting in a brown or grey color
-mutation of tyrosine oxidase prevents any biochemical change and the lack of pigment results in an albino



-mutation of tyrosine oxidase
-can be complete- no pigment in any tissue
-red eyess
-can be partial- where some organs or tissue have pigment


Deficiency of Shared Enzyme

-enzymes are not necessarily dedicated to one pathway
-they may function in multiple different, related or unrelated pathways
-the downside of this is that a single mutation can affect multiple cellular processes


General Clinical Features

-poor growth
-mental retardation
-problems in general metabolism
-neurological problems
-Patient evaluation- clinical picture, onset of MR over time
-Family history- other affected siblings, unexplained infant deaths



-Phenylketonuria (PKU)
-Variant PKU
-defects of tetradhydrbiopterin metabolism BH4
-biochemiical disorders related to the function of pheynlalanine hydroxylase which converts phenylalanine to tyrosine
-clinical heterogeneitiy-three distinct phenotypes from mutation of a single gene


Phenylketonuria (PKU)

-most common of 3
-it occurs when a mutation of phenylalanine hydroxylase prevents conversion of phenylalanine to tyrosine
-accumulation of PHE in cells
-small fraction of PHE may then be converted to phenylpyruvic acid which can be detected in the urine
-autosomal recessive, 1/10,000 live births
-treat by diet modification- early in life, pregnancy


Variant PKU

-between full PKU and non-PKU hyperphenylalaninemia
-required a diet, but not as restrictive as PKU patients


Non-PKU Hyperphenylalanemia

-10 fold increase in PKU levels
-less damaging, but may be benign
-may not requre a special diet


Tetrahydrobiopterine (BH4)

-locus heterogenity- mutations in different genes can lead to the same clinical phenotype
-non-mutant phenylalanine hydroxylase gene
-defect somewhere is Bh4 pathway
-do not respond to PKU diet and develop neurological defects
-BH4 is a cofactor to other enzymes leads to deficit of dopamine and serotonin


Lysosomal Storage Disease

-mutation of a lysosomal hydroltyic enzyme leads to failure of degradation and the accumulation of macromolecules in lysosomes
-over 50
-common: progressive degeneration
-if the macromolecule is not degraded, it cannot be eliminated, so they are stored in lysosomes
-as the organelles become larger, the affected organs and tissues increase in mass
-enzyme replacement therapy


GM2 Gangliosidoses

-GM2 pathway
-three proteins functions together
-alpha, beta subunits and activator


Tay Saches Disease

-autosomal recessive
-rare except for Ashkenazi Jewish population
-3-6 months, death 2-4 years
-deficiency of hexosaminidase A
-inability to degrade GM2 ganglioside
-cherry red spot in retina



-groups of heterogenous disorders
-absence of specific enzyme involved in degradation of glycosaminoglycans
-accumulation of macromolecules in the lysosomes
-not all autosomal recessive, Hunter syndrome is X linked recessive
-permanent, progressive damage
-short stature, delay, skeletal abnormalities and joint stiffness, thickened skin, heart, liver or spleen damage
-bone marrow transplantation, enzyme replacement therapy, gene therapy


Connective Tissue Disorders: Collagen

-osteogenesis imperfecta is due to mutations in type 1 collagen with either reduced collagen production or defective collagens
--4 different classes that range from mild to lethal
-reduced collagen production tends to be brittle bones
-OI type III is perinatal lethal


Ehler-Danlos Syndrome

-error in post translational modification of collagen
-multiple subtypes
-autosomal dominant, autosomal recessive and X linked recessive
-characters: skin fragility, joint hypermobility, skin hyperextensibility
-COL5A or COL3A genes


Marfan syndrome

-fibrillin gene
=primary targets skeleton, eyes, heart
-Marfan patients are tall and thin with very long thin fingers
-they can have joint laxity and scoliosis
-lung problems pneumothorax
-dislocation of the lungs or myopia- cataracts, glaucoma, retinal detachment
-heart issues include mitral valve prolapse, dilation and dissection of the aorta
-the disease is progressive and heart issues become a major threat in the teens



-the presence of 2 chromosomes



-2 chromosomes from the same source (duplication of 1 chromosome)



-2 different chromosomes