Cell And Biology Lecture 7

Front 1

Acute Promyelocytic leukemia (APL)

Back 1

RT between chromosome 15 and 17. Blocks the differentiation of promyelocytes (white blood cell precursors) into mature white blood cells. These patients are at an extremely high risk of developing stroke

Front 2

Chronic Myeloid Leukemia (CML)

Back 2

RT between chromosome 9 and 22. Resulting chromosome referred to as Philadelphia chromosome. Uncontrolled production of maturing granulocytes, predominantly neutrophils, but halso eosinophils and basophils.

Front 3

Dynamic Mutations

Back 3

Mutations that involve the insertion of a repeat sequence either outside or inside the gene. There's a threshold length, if it's below the threshold length = no diesease. If it's above the threshold length = disease.

Dynamic mutations increase in severity and decrease in age of onset in successive generations.

Front 4

Fragile X Syndrome

Back 4

It is a X-linked recessive genetic disorder caused by 200->1000 unstable repeat sequence of CGG outside the FMR1 gene on chromosome X. This mutation ends up causing this FMR1 to be produced, Fragile Mental Retardation gene.

Creates a fragile site on chromosome X that can be observed.

Causes mental retardation, macroorchidism (enlarged testes after puberty), speech delay, behavioral problems (hyperactivity, attention deficit), prominent forehead and jaw, joint laxity, large dysmorphic ears

Front 5

Huntington Disease/Chorea

Back 5

Autosomal dominant genetic disorder. 36- >100 unstable repeat sequences of CAG inside 4pl6.3 chromosome for Huntington protein. This causes an increase production in Glutamine to be inserted into Huntington protein, causes aggregation to form. Inverse relationship between # of CAG repeats and age of onset.

60-100 = juvenile onset
36-55 = adult onset

Front 6

Symptoms of Huntington/Chorea

Back 6

15-18 years after onset, mean survival time
Chorea (dance like movement)
Memory deficits
Affective disturbances
Personality changes
Dementia

Front 7

Haploinsufficiency

Back 7

For most genes, even producing 50% of gene product is enough to remain clinically normal.

But genes that cannot be clinically normal by producing only 50% of of the gene product are called this...Echler-Danlos Syndrome, Marfan Syndrome, Polydactyly.

Front 8

Gain of function mutation

Back 8

Misesense mutation, translocation mutation, dynamic mutation

Front 9

Alpha1 antitrypsin deficiency

Back 9

Autosomal recessive genetic disorder

Caused by missense mutation in SERPINAI gene on chromosome 14q32.1. This gene encodes the serpin peptidase inhibitor alpha 1 (antitrypsin), and this causes methoionie to be replaced with arginine, which can't inactivate elastase. This results in elastase growing, and destroying the ealstin fibers in the lung.

This results in Pulmonary emphysema.

Front 10

Mitochondrial Genome

Back 10

Has it's own DNA, arranged as a circular piece of dsDNA with H and L strands. No introns are present, and they are not protected by histones. Inherited from mother.

DNA/RNA polymerase and enzymes of citric acid cycle are produced on cytoplasmic ribosomes and shipped to mitochondria. For mitochondrial diseases, mutated genes must reach a certain threshold. A women with no symptoms can still pass on the mutated genes to her children and can have affected children.

Front 11

MERRF (MyoclonicEepilepsy with Ragged Red Fibers syndrome)

Back 11

Mitochondrial genetic disorder caused by mutation in tRNAlys gene. A to G (transition) occurs at nucleotide position, causes premature termination of translation of amino acid chain. Large numbers of lysine affects NADH dehydrogenase (complex 1), and cytochrome oxidase (complex 4)

Expression of disease is highly variable.

Front 12

MERRF clinical features

Back 12

Myoclonus (muscle twitching)
Seizures
Cerebellar ataxia
Dementia
Mitochondrial myopathy
Ragged red fibers (irregular shape and blotchy red appearance to the muscle cells)

Front 13

LHON (Leber's Hereditary Optic Neuropathy)

Back 13

Progressive optic nerve degeneration
Leads to blindness, blurred vision, loss of central vision
Enlargement of blood vessels in eyes (telangiectaic microangiopathy)
Affects males more than females

Decrease production of ATP. Cased by 3 types of mtDNA, missense mutations

Front 14

Mitochondrial Genetic Disorders

Back 14

Missense mutations on ND4, ND1, ND 6.

ND4: Complex 1, Subunit 4. NADH dehydrogenase. The most common cause of LHON
ND1: Subunit 1 Complex 1
ND6: Subunit 6. Complex 1

All these mutations decrease production of ATP, affects neurons that require high amounts of ATP.