Mizzou Pathophysiology N3200 Exam 1

Genomics

the study of the multiple genes of an organism and their interactions.

Pharmacogenomics

the study of how genes influence an individual's response to medications.

DNA

Double-helical structure composed of nucleotides

Nucleotide

pentose sugar

Nitrogen bases

DNA = Adenine

RNA = Adenine

Uracil

Transcription

DNA ---> RNA

DNA synthesizes RNA within the nucleus

RNA = mirror image of DNA

RNA is ONE strand

Gene

Specific group of nucleotides of the DNA helix that carries a code for protein

Exon = protein coding sequences

Intron = sequences with NO code

Codon

gene arrangement of three specific nucleotide bases

-- contains directions for synthesis of a specific amino acid

Mutation

can be inherited of sporadic

Somatic cell mutation

not inherited

Germ cell mutation

inherited

Labeling a gene

chromosome #

Karyotype

appearance and number of chromosomes of an individual

Chromosomes

-23 pairs of chromatids = 46 chromosomes

-22 are somatic cell chromosomes

-23rd pair includes sex chromosome

Structure = two chromatid strands connected by a centromere

Allele

corresponding genes on each chromatid

Homozygous

both alleles on each corresponding chromosome are the same

Heterozygous

the alleles on corresponding chromosomes are NOT the same

Dominant vs Recessive

An allele can carry a dominant trait or a recessive trait

(brown eyes = dominant and blue eyes = recessive).

Phenotype

how the gene mix is manifested in the individual

Genotype

the genetic makeup of a person (B-B or B-b > brown eyed person)

Penetrance

ratio of how many persons with the phenotype have the genotype

example:

if a women has the BRCA (breast cancer gene) there is an 85% chance of getting breast canver; this gene is highly penetrant

Expressivity

a disorder can be expressed more or less severely in different individuals

example:

a person may have a gene for familial hypercholesterolemia but can have a mild or severe form of the disease

Multifactorial Inheritance

a disease is caused by a combination of inherited susceptibility and environmental factors that trigger a disorder

Example: Diabetes and cancer

Single Nucleotide Polymorphisms (SNP)

A mutation in one nucleotide of a gene sequence

Example: Normal Nucleotide ACTTG but disease nucleotide sequence is ACTGG

Mitochondria

-have their own ribosomes and DNA that regulate energy production

-theorized to be independent

bacteria-like organisms that became incorporated into human cells

-during fertilization

the ovum destroys the sperm mitochondria

-All mitochondria DNA is derived from mother

-Maternity tests can be based on mitochondrial DNA

DNA alteration

-changes in nucleotide sequences as well as deletions or insertions of nucleotides

--these changes can represent the change of base sequences in a codon

leading to a change in the protein structure

Example:

sickle cell anemia

Oncogenes

cancer causing genes

-- can be inherited or acquired

Activated oncogene

I. undergoes transcription

II. the ribosomes

in turn

III. Oncoproteins will direct the cell to undergo uncontrolled proliferation

persistent mitotic divisions

Tumor suppressor gene

genes inhibit uncontrolled cellular mitosis and lead to persistent proliferation

Example:

p53 tumor suppressor gene stops the mitotic cell division cycle... when defective tumor suppressor genes do not suppress cancerous transformation of cells and cancer growth occurs uninhibited.

Cancer caused by Virus

Another way that cancer occurs is through viral insertion of an oncogene

For example:

-The human papilloma virus (HPV) inserts its DNA into the DNA of cervix cells. When activated

this DNA stimulates the abnormal growth cycle associated with cancer cells

--Additionally

it inhibits the action of p53

This is the mechanism for the development of cervical cancer from HPV infection

Knudson's "Two Hit" Hypothesis

pairs of alleles make up an individual's genotype

--if one of the alleles of a pair is damaged or mutated then the normal corresponding allele can counteract the effect in most cases

example:

I. the initial allelic mutation is the "first hit"

II. cancer only developed in persons who acquired a second allelic mutation "second hit"

Aneuploidy

abnormal number of chromosomes

Example: trisomy 21

Translocation

when one part of a chromosome breaks off and connects to another chromosome

Mosaic

occurs when there are cells with different numbers of chromosomes within the same individual

Molecular Analysis

acquired genetic alterations

- Polymerase chain reaction (PCR)

- Fluorescence in situ hybridization (FISH)

- Sothern blotting

Tests that can be done prenatally

-chronic villus sampling (CVS) 10 to 12 weeks

-Amniocentesis 16 to 18 weeks

-ultrasound

-Percutaneous umbilical cord blood sampling

Who should be offered prenatal screening?

-Women 35 years or older

-Abnormal ultrasound findings

-Couples who are close blood relatives

-Women with conditions such as diabetes

can be associated with an increased risk of fetal problems

-Ethnicity

-Unexplained or multiple miscarriages

-Family history of an inherited condition

intellectual disability

Maternal Serum Screening

Proteins that are produced by the developing placenta and fetus enter the mother's blood:

- AFP (alpha-fetoprotein)

- hCG (human chorionic gonadotropin

- uE3 (unconjugated estriol)

- DIA (dimeric inhibin A)

---- If test is positive then it indicates an increased chance of fetal problems

Familial Hypercholesterolemia

- Absent or dysfunctional LDL receptors

- Mutation > 19p gene locus

-LDL can NOT be taken up into liver (like normal) because liver lacks LDL receptors with this condition. In addition to this LDL and cholesterol manufacture is NOT suppressed so the same amount is being produced.

Homozygous form of Familial Hypercholesterolemia

SEVERE total cholesterol levels 600 to 1000

Heterozygous Familial Hyperchoolesterolemia

Less severe total cholesterol levels 200 to 400

Familial Adenomatous Polyposis

Autosomal dominant condition

-- An Individual that is born with APC allele needs to have another allele mutate in order to develop disease (two hit)