434 Unit 2 Lec 9-10

What is biotechnology

 the application of recombinant DNA and sequencing technology for the manipulation of biological materials

→ Applied to human health, agriculture, biofuels and exotic pet industries

challenges associated with the production, approval, and  use of protein based drugs

•Increased complexity is a challenge in terms of production, delivery, development cost

Old school gene therapy

Patient tissue sample → look under microscope

Old-ish school gene therapy

Patients tissue or blood → Proteonomics, genomics

Current School gene therapy

•Next generation sequencing 

→easily/rapidly sequence entire human genomes

→determine which genes are active under given disease state

→Identify rare variants in cancer

What is DNA

→ Molecule that contains biological instruction that make each species unique

→ Passed from adult to offspring

Where is DNA found in eukaryotes

DNA is found in the nucleus and mitochondria

Where does all mitochondrial DNA come from

Female parent

What is DNA made of

•Made up of nucelotides with a sugar phosphate backbone

•Nitrogenous bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C)

What are gene variants

•Permanent change in DNA sequence of a gene

**•Does not always cause disease- disease causing variants are uncommon**

Substitutions

•Replaces one nucelotide with another

•Silent, mussense and nonsense

•Silent variants change DNA and mRNA but not protein

•Nonsense makes a STOP codon

•Missense is a nucleotide change that results in a protein change and the change **may** alter protein function

Insertion

•Adds one or more nucleotides to the gene

\*Often results in frameshifts

Deletion

•Deletes one or more nucleotides from the genes 

\*Often results in frameshifts

Indel

When insertions and deletions occur at the same time, must be larger than a single substitution

Duplication

 When a stretch of nucelotides is copied and repeated next to the original sequence; duplications often take the form od repeat expansions 

Copy number variations

•Some genomes contain fewer or many more than two genes = copy number variation (CNV)

•Caused by large scale insertions, deletions or duplications

•Can affect risk of disease or response to drugs 

Aneuploidy

Change in the number of chromosomes from 46 

Translocation

When part of a chromosome breaks off and attaches to another chromosome

Hereditary variants

Variants passed from parents to child

→Present in nearly every cell in the body

→Also called germline variants

Non-Inherited variants

variants that occur during a person’s lifetime

→Can’t be passed on

→Not present in every cell

→AKA somatic variants 

Mosaicism

When certain cells don’t have the same genetic makeup

→Occurs after fertilization

→Could be germline or somatic 

Autosomal dominant

•One altered copy is sufficient to cause disorder

•Can be inherited or can arise from a new variant

Ex: Huntington’s

Autosomal Recessive

•Variants in both copies are required for the disorder to manifest 

•Individuals with one variant have few or no symptoms 

•Typically not seen in every generation

Ex: sickle cell, cystic fibrosis

X linked dominance

•Caused by gene variants on the X chromosome

•Males and females who inherit an X with a variant will show the disorder

•Females may show less effect

•Father’s cannot pass X linked traits to sons 

X linked recessives

•Females: need variants on both X chromosomes

•Males: only need one variant 

•father cannot pass X linked traits to son 

Y linked

•Variant on Y chromosome

•Passed from father to son 

Codominant

•Two different varianta of the same alleles are expressed that make different proteins 

•Both variants influence the traits

Mitochondrial

•Variant occurs in mitcohondrial DNA \n •Also known as maternal inheritance

•Only egg cells contribute mitochondria to the embryo