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Flashcards in MCP 1 Deck (27):

Define Human genetics

the study of heredity in man and WOMAN


Define medical genetics

the study of human genetic variation of medical significance


Subunits of medical genetics

1. clinical genetics-diagnosis
2. genetic counseling-information
3. molecular genetics - lab
4. biochemical genetics - lab
5. cytogenetics - lab


Define mutation

-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


Identify the two patterns of inheritance

dominant vs. recessive
autosomal vs. X-linked


define inherited disease

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


define acquired disease

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



a set of characteristics which occur together and are assumed to have a common basis
-not all character occur in all affected individuals (example VCFS)
-range of variability within a population


define biochemical genetics

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


Define in-born errors of metabolism

genetically determined biochemical disorder in which a specific enzyme defect produces a metabolic block leading to either..
-accumulation of substrate
-deficiency of products



deficiency in homogenstic acid oxidase -> leading to the accumulation of homogentisic acid in the blood; damage to cartilage, heart kidney -> arthritis in 30s



deficiency in tyrosine oxidase -> lack of melanin production and lack of pigmentation -> can be either partial or complete


salvage pathways

can spare the over accumulation of potentially toxic substances in cells - and make other by products with the accumulated intermediate


List some characteristics of in-born errors of metabolism

-single enzyme defect


General clinical features of in-born errors of metabolism

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



PKU->defect in phenylalanine hydroxlase
abnormal PKU -> defects in tetrahydrobiopterin metabolism
- the pheylalanine builds up and a small amount is converted to pheylpyruvic acid which can be detected in urine



1/10,000 live births
autosomal recessive
treat by modifying diet -> early in life and in pregnancy


non-PKU hyperpheylalaninemia

-10 fold increase in PHE levels
-less damaging
-may not require a special diet


Variant PKU

-between full PKU and non-PKU hyperphenylalaninemia
-requires a diet, but not as restrictive as PKU pateints


Lysosomal storage diseases

-autosomal recessive
-mutation of lysosomal hydrolytic enzymes leads to failure of degeneration and the accumulation of macromolecules in lysosomes
-over 50 known deficiencies
-clinically heterogeneous
-common presentation; progressive degeneration


Tay Sachs Disease

-autosomal recessive
-rare except in Ashkenazi jews (carrier frequency 1/27)
-onset 3-6 months
-death by 2-4 years of age
-inability to degrade GM2 ganglioside
-deficiency of hexosaminidase A
-inability to degrade gangliosides GM2
-no known treatment
-clinically significant finding is the cherry red spot in the eye (retina)


Define Mucopolysaccharidoses

-group of heterogeneous disorders
-absence of specific enzyme involved in degradation of glycosaminoglycans (degradation requires stepwise removal of subunits so if one enzyme is missing along the chain the chain will not be degraded and this product will accumulate)
-accumulation of macromolecules in the lysosomes


Clinical features of Mucopolysaccharidoses

-permanent, progressive damage
-short stature, delay, skeletal abnormalities and joint stiffness, thickened skin, heart liver or spleen damage


Treatment for Mucopolysaccharidoses

-bone marrow transplant
enzyme replacement therapy
gene therapy


Osteogenesis imperfecta

-connective tissue disorder
-due to a defect in type 1 collagen
-autosomal dominant
-four different classes range from mild-> lethal
a) type II is perinatal lethal
b) type IV is mild to moderate bone deformity and fracturing
c) Type III is more severe -intermediate between II and IV


Ehler-Danlos Syndrome

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


Marfan Syndrome

-a connective tissue disorder
-related to a mutation if fibrillin gene
-primary defects seen in skeleton, eyes (lens displacement), lung (pneumothorax) and heart (dissection of aorta)
-patients have very long, thin fingers, with joint laxity and scoliosis
-no known treatment but being aware of diagnosis is key to manage symptoms and limit stressful activities