Chapter 1: The Cell as a Unit of Health and Disease
• General Concepts
o Pathology
The Greek word meaning suffering
Modern meaning “study
... [Show More] of disease”
• Understanding the cellular and molecular abnormalities that give rise to disease
o Understanding NORMAL cellular structure and function is integral to understanding pathology
The focus of this initial lecture
o “Physiologic process” generally means a normal process
Example – physiologic jaundice
• Expected
o “Pathologic process” generally means an abnormal process
Example – pathological jaundice
• The Genome
o Sequencing of human genome began in the 21st century
3.2 billion DNA base pairs
o The cost of sequencing is significantly decreasing
o Computers allow for analysis of vast amounts of data to help our understanding
o Our understanding of health and disease is significantly increasing
Complexity of disease is being revealed
o Genes carry all information for making proteins required by the body for growth and maintenance
o Cancer treatment – fine tuning
o Psychological – some people not responsive to SSRI
May not have the receptor for those drugs to work
• How the genome becomes “us”
• Histones
o 174 base pair DNA segments wrapped around a central core of proteins called Histones – this is a nucleosome
Look like beads that are linked by short DNA linking segments
o This entire structure is called chromatin
o How chromatin is compacted and wound around varies in different genomic regions
Heterochromatin – Inactive for transcription
• DNA material cannot be replicated
Euchromatin – Active for transcription
These stain different colors
• Noncoding DNA
o Approximately 20,000 protein-encoding genes in the genome
Only about 1.5% of entire genome (so, 98.5% of genes are not encoded)
• Bulk of it is not encoded
o These protein-encoded genes are the foundations of cells
Cells function as enzymes, structural elements, and signaling molecules
o Non-coded regions of the genome are the critical “architectural planning”
o Classes of these include the following
Promoter and enhancer regions that bind protein transcription factors
Binding sites for proteins that organize chromatin structures
Non-coding regulatory RNA – regulate gene expression
Mobile genetic elements (i.e. transposons)
• Aka “jumping genes” Move around the genome to regulate genes and organize chromatin
Special Structure Regions of DNA
• Telomeres (chromosome ends) and centromeres (chromosome tethers in center)
o Polymorphisms (genetic variations) associated with disease are located in the NON-PROTEIN CODED Regions of the genome
So…. What does this mean??
• Cause of disease may be more related to variation in GENE REGULATION rather than structural changes in proteins
• The 98.5%
• Focus was once on coded regions – now is regulation
o Also, interesting fact….
Any two humans are ~99.5% DNA identical and 99% DNA sequence identical to chimpanzees!!!!
SO, our individual variations is encoded in 0.5% of our DNA
• This is still approximately 15 million base pairs
o Imagine how many genes are out there!!!!!!!!!!!! It’s like a universe!
• Polymorphism
o Alterations in DNA sequence do not, alone, explain the phenotypes in human population
Remember: phenotype is the expression of a trait; observable features
o Rather, may be explained by Epigenetics
WHAT IS THAT??
• Heritable changes in gene expression that are not caused by alterations in DNA sequence
• Can be altered by medicine
• Cellular Housekeeping
o Many housekeeping functions are within the membrane-bound intracellular organelles
o This allows potentially injury producing enzymes or reactive metabolites to be stored in high concentrations without risking damage to other parts of the cell
o Rough Endoplasmic Reticulum (RER)
Synthesizes new proteins for plasma membrane or for secretion
Production sight
o Golgi Apparatus
Physically assembles proteins synthesized above
RER Golgi Apparatus [Show Less]