NURS 220 - Genetics and mutations

What is DNA?

chemical blueprints affecting how the body looks and functions

How does DNA looks (characteristics)?

double stranded spirals of base pairs, complementary pairing

What are Genes?

genes are segments of DNA

How do Genes differ from each other?

Human genome contains different protein-coding genes, each differ in “recipes” which is for a specific feature based on dominant and recessive genes

How does Genes characterize cells?

all are selectively expressed to determine cell structures and function; cells must be able to change expression of certain genes to respond/adapt to changes in cellular environment

What are Chromosomes?

chromosomes are genetic bundles

How many Chromosomes are in human cells?

46 chromosomes - 23 pairs - 22 autosome and 1 sex chromosome; Gametes (ova and sperm) only have one of each chromosome - 23 singles

What is Epigenetics?

the environment (temp, radiation, food, drugs, nutrients) produce immediate effects tjat can be imprinted long-term

DNA Repair - What is it?

cells mechanism to detect and repair various damages to DNA (environment or replication errors)

DNA Repair - What regulate/controls it?

control of DNA repair is closely tied to regualtion of the cell cycle

DNA Repair - Checkpoints

checkpoint mechanisms ensure that cells DNA is intact before permitting DNA replication and cell division to occur

DNA Repair - Checkpoints: Proof reading

corrects errors during DNA replication; Polymerase adds incorrect nucleotide → polymerase detects bases are mispaired → removal of incorrect nucleotide

DNA Repair - Checkpoints: Mismatch repair

fixes mis-paired bases right after DNA replication; Mismatch in DNA → DNA strand is cut and mismatch pair and its neighbors are removed → Missing patch is replaced with correct pairings → DNA ligase seals the gap

DNA Repair - Checkpoints: DNA Damage repair pathways

detect and correct damage throughout the cell cycle; Damage to the DNA strand → Detection → enzymes cut the damage region out → DNA polymerase replaces pairs and ligase seals backbone of DNA

DNA Repair - How do mutations occur?

when theres a failure in checkpoint leading to accumulation of damage → Mutations

Genetic Mutation - What is it?

Permanent alteration in DNA sequence

Genetic Mutation - Vary in size

DNA base, single gene, entire chromosome

Genetic Mutation - Occurrence Varies

present in all cells, present only in an egg or sperm cell, present in single cell and multiplies

Genetic Mutation - What are the 2 classifications?

Inherited and Acquired (somatic)

Inherited Genetic Mutation - Where does it occur?

typically in every cell in the body

Inherited Genetic Mutation - When does it develop?

present through a persons life

Inherited Genetic Mutation - How is it developed?

passed on in parent egg and/or sperm cells

Acquired Genetic Mutation - Where does it occur?

occurs in individual cells

Acquired Genetic Mutation - When does it develop?

May develop at any time during a persons life

Acquired Genetic Mutation - How does it develop?

related to error during cell division when DNA get duplicated or when DNA gets damages by environmental factors (UV, chemicals, viruses, teratogens)

Inherited and Congenital Mutations - Single Gene

autosomal dominant, autosomal recessive, sex-linked

Inherited and Congenital Mutations - Chromosomal

deviation ins structure or number of chromosomes; gene loss, addition, exchange, or rearrangement

Inherited and Congenital Mutations - Multifactorial

genetic predisposition or susceptibility; caused by both genetic and environmental factors

Gene Mutations - Autosomal Dominant

only need present on one side of gene pair to manifest

Gene Mutations - Autosomal recessive

must be present on both sides of gene pair to manifest

Gene Mutations - Sex-linke

gene mutation specific to X or Y chromosome (23rd pair)

Chromosomal Mutations - Translocation

piece of one chromosome break off and attaches to another chromosome; not aligning properly

Chromosomal Mutations - Deletion

chromosom breaks and some genetic material is lost; elimination of portion

Chromosomal Mutations - Duplication

part of a chromosome is duplicated too many times; extra

Chromosomal Mutations - Inversion

breakage of a chromosome in 2 places; resulting piece of DNA is reversed and re-inserted into the chromosome; flipped upside down

Commonly inherited Genetic mutations

baldness, heterochromia, asian flush, freckles, cleft chin, dimples, blue eyes, red hair, albinism, color blindness, lactose intolerance

Inherited Conditions (genetic mutations)

celiac disease, cleft lip/palate, cystic fibrosis, Huntington disease, down syndrome, muscular dystrophy, marfan syndrome, hemophilia, phenylketonuria, turner syndrome, sickle cell anemia, tay-saches disease

Prenatal Screening - Purpose

minimize or prevent certain conditions

Prenatal Screening - What factors increase risk for congenital disorder?

known carrier of recesive genetic disorder, family Hx of congenital disorder, maternal age >35 y, chromosomal disorder in previous pregnancy, neural tube anomalies in previous pregnancy, teratogen exposure

Chromosomal Mutations -

Screening and diagnostics - what are they used for?

physical exam methods to identify risk for or presence of genetic disorders

Screening and diagnostics - what are the methods/options?

ultrasound, blood testing, tissue biopsy, fetal call testing (Amniocentesis - needle to fetus for amniotic fluid, CVS biopsy - chorionic villus sampling), unbilical cord blood testing, embryoscopy

TORCH Screen - Method

prenatal blood test

TORCH Screen - What is it used for?

screen diseases that can cross the placenta and cause birth defect in newborn

TORCH Screen - What are the disease screened for?

cataracts, deafness, intellectual disability, heart problems, seizures, jaundice, low PLT levels

TORCH Screen - What does TORCH stand for?

Toxoplasmosis, Other (HIV, HPV, varicella, syphilis), Rubella, Cytomegalovirus, Herpes simplex

Genetic Treatment Methods - In vivo

treatment injected into host

Genetic Treatment Methods - Ex Vivo

sample taken from host and treated outside - in test tube

Non heritable gene editing

when genetic editing is not done to the reproductive cells, so cannot be passed to offspring

Heritable gene editing

when genetic editing is done to reproductive cell and early stage embrios, so it can be passed to offspring

Luxturna tx - what is it?

benign viral vector deliver a gene into the eye of patient from a rare disease; first true egen thrapy as viral treatment is delivered directly to patients body

CRISPR - What does it stand for?

Clustered Regularly Interspaced Short Palindromic Repeats

CRISPR - What is it?

biotech tool that allows for precise cutting “editing” the DNA of any living organisms

UCLA impact on CRISPR and Cystic Fibrosis

UCLA developed inhalable nanoparticle-based CRISPR therapies that directly deliver gene-editing materials to lung epithelial cells via aerosol spray; minimal inflammatory response and near-normal mucus clearance and lung function