Prevalence - One in every 12-13 people, dont know they have it.
Incidence - About 650k new cases each year.
Impact leading cause of renal failure, blindness and amputations. 17% of health
care costs used by diabetics.
First described as a clinical syndrome with infants having dehydration, hypochloremia,
An inherited autosomal recessive genetic disorder.
Most common life threatening disease in Caucasians.
The CFTR channel is a chloride
Genomes and Medicine
SNP genotypes do not provide useful clinical information for a majority of
Diagnosis of phenylketonuria at birth or BRCA1/2 mutation in adulthood can
have management benefits.
Prenatal Genome Sequenci
Mitochondrial Disease Genetic defects affecting cells ability to make ATP. Mutations
can be on mtDNA, or nuclear DNA.
Principles of Maternal Inheritance
Asexual inherited from mother.
Heteroplasmy segregation of mitochondria rando
Forensic Use of DNA
Forensic DNA Techniques
1. Short Tandem Repeats (STR)
Amplify DNA using PCR with fluorescent primers.
Separate fragments using electrophoresis.
Record fluorescence using laser.
Calculate probability of match based on chance.
Epigenetics mitotically or meiotically heritable changes in phenotype that are not based
on the DNA sequences.
Different cell types in the body have different phenotypes but are genetically
When a human cell divides, the phenotype
Gene Therapy addition of DNA or RNA to cells to:
1. Provide functional copy of missing or defective gene.
2. Inhibit defective gene.
3. Protect against infection
4. Activate immune response
5. Kills cells
6. Make cells grow
DNA Replication and Repair
Origins of replication are not active at the same time during DNA replication
DNA synthesis begins with RNA primer.
FEN1 endonuclease removes the primer.
DNA pol delta is the main DNA pol.
DNA pol gamma has
Mutation and Genetic Code
AUG is the start codon and it codes for methionine.
Where translation starts determines the reading frame.
STOP codon ends translation.
There are 20 amino acids, the ones that are used more frequently are encoded
Human Genome Projects
Human Genome Project used a hierarchical shotgun sequencing approach.
The human genome only contains about 22k protein coding genes.
Interspersed repeats LINEs, SINEs, RNA and DNA transposons comprise about
45% of genome.
Overview of mRNA Processing: 2 Processing Events
Position of Tx Initiaion
The position of transcription initiation can be modulated by multiple promoters or
multiple start sites from one promoter.
A 5 cap is added to the 5 end immediatel
Gene structure and Function
RNA pol read template DNA from 3 to 5 and synthesize 5 to 3.
No primer required.
Local unwinding of DNA aided by DNA topoisomerases.
Structure of the gene or transcription unit
Tx start promoter
Nucleosomes composed of 8 histones wrapped around by 146 bp DNA.
Metacentric equal arm length.
Submetacentric one arm shorter than the other.
Acrocentric one arm much shorter than the other.
Meiosis cell division by which germ ce
Intro the Microanatomy
Microanatomy study of the body at the microscopic level.
Cells are membrane bound compartments divided into domains called organelles.
Cells are organized into tissues.
Tissues are an aggregation of related cells with their specifi
Compund heterozygote Genotype with 2 different mutant alleles at the same
Expressivity The degree of severity of a trait by someone who has a genetic
Founder effect High frequency of a mutant allele in
Caused by mutations in the gene encoding the first enzyme in the beta oxidation
of fatty acids.
Sudden death, SIDS, cardiomyopathy, skeletal myopathy.
Treatment with very low fat diet, medium chain triglycerides, fasting avoida
Major areas of Practice
Prenatal and Preconception
Advanced maternal age mother over 35.
Abnormal prenatal screening, serum makrs or ultra sound.
Two or more pregnancy losses.
Totipotent multipotent unipotent fully specialized.
Regulation of Cell Differentiation
When cells reach terminal differentiation, they have lost their ability to divide by
Determination when there is expression of specific
Membranes in Cells
Made up of glycospingolipids and protein receptors organized in microdomains.
Smallest filaments of the cytoskeleton, also most abundant.
Composed of actin.
Actin joined together to form a twisted double helix.
Self assemble without using energy, disassembly requires ATP.
Peroxisomes and Mitochondria
Peroxisomes responsible for breakdown of peroxide, fatty acids, detox, and synthesis
of cholesterol, bild acids, and myelin.
Small and spherical.
Single lipid bilayer.
Granular matrix due to enzymes.
Stem Cells and Regenrative Medicine
Undifferentiated but capable of giving rise to all cell types of the organ/tissue.
Can divide indefinitely.
Balance between self-renewal and differentiation.
Maintained within a specialized tissue enviro
Endocytosis, Lysosomes and Trafficking
Pinocytosis cell drinking, non specific.
Micro and Macropinocytosis.
Caveolae form and bud off to form vesicles rich in caveolin.
Not completely random, cell membrane is negatively charged so it attrac
Ionic Equilibrium and Resting Membrane Potential
Cyctic Fibrosis Connection:
Three major clinical symptoms
elevated NaCl in sweat,
abnormal mucus secretion that lead to COPD and pancreatic insufficiency
infection of respiratory system by Pseudomonas ae
The primary extracellular cation and determines ECF volume.
Ingested Na stays in the ECF because Na pumps keep it out of ICF.
Low dietary Na can lower ECF volume and blood pressure.
Low Na/volume sensed by baroreceptors
Membrane Transport Mechanisms
The Structure of Cell Membranes
The cell membrane has a lipid bilayer that is attached with proteins.
Transport mediated by membrane proteins is called carrier mediated transport.
Active and Passive Transport
Protein Synthesis and Secretion
Components: proteins and rRNA.
Two types: free or bound to membrane of the RER.
Polyribosome a single strand of mRNA with many ribosomes attached.
Proteins made on free ribosomes are for intracellular use, not sec
I. Compartmental Organization of the Body
Molarity (molar concentration): concentration relative to molecular weight and
total volume. C= n/V
Osmoles: number of solute particles. Mmol x number of particles.
Osmolality: solute particles/1
Nuclear Envelope A 2 membrane system that encloses a perinuclear cisterna and
consists of inner and outer nuclear membrane that is connected by nuclear pore
Nucleolus synthesis of rRNAs and assembly of ribosomal subunits.