Robbins and Cotran 9th Edition Questions

Chapter 1: The Cell as a Unit of Health and Disease

Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury and Death

Short Answer Questions

What are the four aspects of a disease?  1. Etiology Genetic - Inherited mutations and disease-associated gene variants, or polymorphisms Acquired - Infectious, nutritional, chemical and physical. 2. Pathogenesis - The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent. 3. Morphological changes - The structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process. 4. Clinical Manifestations - Symptoms and signs of disease, as well as its clinical course and outcome

Chapter 3

Chapter 4

Chapter 5

MC cause of spontaneous abortion is ?
A demonstrable chromosomal abnormality.

1% of all newborn infants possess a gross chromosomal abnormality and 5% of people <25y present with
a genetic disease.

Mutation
permanent change in the DNA, if affect germ cells are transmitted to the progeny

List and describe 4 broad categories of human genetic disorders:

[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance ii. Often highly penetrant (large proportion of pop with gene has disease) b. Chromosomal disorders i. Structural or numerical alterations in autosomes and sex chromosomes ii. Uncommon, high penetrance c. Complex multigenic disorders i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present d. Single gene disorders with nonclassic patterns of inheritance (not mendelian) i. Disorders resulting from triplet repeat mutations ii. Mutations in mitochondrial DNA iii. Those influenced by genomic imprinting iv. Those influenced by gonadal mosaicism]]

List and describe the possible outcomes of a point mutation in a coding region?
[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid, b. Nonsense mutation – makes a stop codon ]]

List and describe the possible outcomes of point mutation or deletion in a non-coding region.
[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing > failure to make mature RNA > no translation]]

List and describe the possible outcomes of deletions and insertions.
[[a.Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene ]]

List and describe the possible outcomes of trinucleotide repeat mutations.
[[a. Usually G&C, dynamic and increase during gametogenesis, “RNA stutters”,b. Fragile X – CGG 250-4000, Huntinton’s Disease ]]

List and describe three examples of inheritance of single gene mutations

[[a. AD – manifested in the heterologous state, one parent of index case is usually affected, males and females affected and both can transmit conditioni. De novo cases may not have affected parentii. Penetrance = fraction of people with gene who have the traitiii. Variable expressivity = those with mutant gene have variety of phenotypesiv. Often age of onset is delayed so can reproduce before die from diseasev. Biochem mechanisms1. Reduced production of a protein or dysfunctional/inactive protein2. Involved in regulation of complex metabolic pathyway subject to feedback inhibition3. Key structural proteins (collagen and cytoskeleton of RBC)a. May be a dominant negative , e.g. osteogenesis imperfecta4. Gain of function are rare, 2 formsa. Increased in proteins normal function (excess enzyme activity)b. Huntinton’s diseas (abn protein accumulates, toxic to neurons)b. ARi. Largest category – both alleles at a locus are mutated1. Expression is uniform, complete penetrance common, early onset, unaffected carrier family members, mostly enzymesc. X Linkedi. All sex linked, and almost all are recessive , if Y Chromosome affected usually infertile males > no progenyii. Male expression b/c hemizygous, daughter carriers with variable phenotype because of lionization of 2nd X e.g G6DPiii. Dominant . vitamin D resistant rickets]]

Stopped at P142

Chapter 6

Chapter 7

Chapter 8

Chapter 9

Chapter 10

Chapter 11

Chapter 12

Chapter 13

Chapter 14

Chapter 15

Chapter 16

Chapter 17

Chapter 18

Chapter 19

Chapter 20

Chapter 21

Chapter 22

Chapter 23

Chapter 24

Chapter 25

Chapter 26

Chapter 27

Chapter 28

Chapter 29