Genetics and Cellular Biology

Epigenetic Processes

-Epigenetic changes do not alter DNA sequences, but the patterns of gene expression +Chemical and structural changes alter the availability of genes to be transcribed and expressed +Covalent modifications: methylation, acetylation, chromatin remodeling, ubiquitination

Multifactorial Disease: Breast Cancer

5-10% of all breast cancer cases are inherited BRCA1 and BRCA21800 known mutations in gene; Autosomal Dominant Inheritance. You inherit the mutation, not the disease With a BRCA mutation: 60% will be diagnosed with breast cancer by 50 years of age and 80% by 70 years of age.

Mutagen

A chemical or agent that results in changes of form or function following exposure

Chromosomal disorder

A deviation in the number or the structure of chromosomal, such as trisomy 21

Cytoplasm

A jellylike fluid inside the cell in which the organelles are suspended

positive feedback

A type of regulation that responds to a change in conditions by initiating responses that will amplify the change. Takes organisms away from a steady state.

ANEUPLOIDY

Abnormal number of chromosomes

Loci

Address on a genome where an allele resides Starts with chromosome # Followed by p or q. Ends with numerical "address"

Allele

An alternative form of a genetic locus; a single allele for each locus is inherited from each parent

Autosomal dominant

An observable phenotype characteristic that requires one copy of an allele

Autosomal recessive

An observable phenotype characteristic that requires two copies of an allele

Chromosomal disorders

Any deviation from the structure and number of chromosomes Errors during meiosis lead to defective gametes 1/200 live-born infants Some deviations cause fetal death

Golgi Apparatus

Associated with ER, "packaging"

Basic Cell Functions

Basic unit of lifefunctions to promote survival Obtains nutrients and O2 from surrounding environment; Converts nutrients and O2 into energy; Eliminates waste products from these conversions; Synthesizes proteins for cell structure, growth, and function; Controls the exchange of materials in and out of cell; Moves materials around within the cell itself; Controls (to some extent) the environment surrounding it; Reproduction (except in the case of nerve or muscle cell loss from disease or trauma).

Lysosomes

Breakoff from Glogi, "intracellular digestive system" for 1) damaged cell structure, 2) food particles, 3) unwanted pathogens (bacteria)

Recombination: Genetic Variation

Chromosomal Recombination occurs during meiosis Only Rule: Each gamete has 1 copy of each autosome and 1 sex chromosome Gives rise to genetic variation

Rough ER

Contains Ribosomes -> Protein synthesis

Nucleus

Control Center of cell Contains cellular DNA DNA-RNA-Protein Some cells (skeletal muscle) mutli-nucleated Controls mitosis (cellular reproduction)

Central Dogma of Molecular Biology

DNA -> RNA -> Protein DNA transcribed to RNA translated Protein.

many genes essential to rapid cell division in the embryo must be silenced in adults

DNA damage +Cellular insults/damage are routine +Can leave lasting effects in form of epigenetic modifications Environmental Stimuli +Nutrition, physical activity, drug use +In Utero environment

Chromosomes

Each human somatic cells has 46 chromosomes 22 pairs of autosomes 1 pair of sex chromosomes (X and Y) Every somatic cell contains 2 alleles for each gene Alleles that are the same - homozygous Alleles that are different - heterozygous

Secondary

Energy from ion differences

Specialized cell functions

Glands in digestive system secrete digestive enzymes (protein producing abilities)

Biological Negative Feedback

Human body temperature - The hypothalamus of a human responds to temperature fluctuations and responds accordingly. If the temperature drops, the body shivers to bring up the temperature and if it is too warm, the body will sweat to cool down due to evaporation. Human blood pressure - When blood pressure increases, signals are sent to the brain from the blood vessels. Signals are sent to the heart from the brain and heart rate slows down, thus helping blood pressure to return to normal. When a human is hungry, metabolism slows down to conserve energy and allow the human to continue living with less food. Regulation of blood sugar in humans - When blood sugar rises, insulin sends a signal to the liver, muscles and other cells to store the excess glucose. Some is stored as body fat and other is stored as glycogen in the liver and muscles. Production of human red blood cells (erythropoiesis) - A decrease in oxygen is detected by the kidneys and they secrete erythropoietin. This hormone stimulates the production of red blood cells.

Narcotics/heroin

IUGR, neonatal withdrawal

Marijuana

LBW, neurobehavioral problems Spermabnormalities

Homeostasis

Maintenance of a constant & "normal" internal environment

Other "environmental" causes of congenital defects

Malnutrition, deficiency of various vitamins Ingestion of toxins or vitamins that are teratogenic in excess (mercury, vitamin A) Infections in pregnant mother that are passed to the fetus

Diffusion

Movement of molecules from an area of higher concentration to an area of lower concentration.

Smooth ER

No Ribosomes -> lipid synthesis

Simple Diffusion

No carrier protein required. Occurs through intermolecular spaces. Must be lipid soluble.

Genetic Variations

No disease Eye color Hair color Genetic Disorders Muscular Dystrophy Sickle Cell Anemia Risk Factors Diabetes Hypertension

DNA-RNA-Protein

Nuclear DNA directs the synthesis of certain proteins that determine the specificity of the cell; Genetic code for a specific protein is transcribed into messenger RNA; mRNA exits the nucleus and delivers the code to ribosomal RNA; rRNA reads and translates the code into appropriate amino acid sequence for any given protein; Transfer RNA then delivers these sequences within the cytoplasm to their designated site.

Cell membrane (a.k.a. Plasma membrane)

Phospholipid Phosphate Lipids Selectively permeable Fluid Mosaic Model

Point mutations

Point mutations can occur in somatic or germline cells Mutations in germline cells become part of the offspring's genetic templates Chromosomal disorders and point mutations can affect gene expression

Multifactorial Disease

Polygenetic conditions are those in which a number of genetic variants are associated with increased risk or prevalence of the disease.

Multifactorial Disease

Polygenetic,Gene x Environment,Cancer, T2DM, CVD/CAD, Respiratory, Alzhiemer's

Mitochondrion

Powerhouse of the cell, majority of cellular energy production (ATP), self-replicative, contains own DNA Derives energy from nutrients and converts it to a useable form (ATP) to support cellular activities; Number of mitochondria per cells varies (100-2000) according to the energy needs of the cell;

Allostasis

Process of achieving stable, homeostatic, environment

Primary

Requires ATP. (Na+/K+ pump)

What is EPIGENETICS?

Study of non-DNA sequence-related heredity The influence of environment and choices on your genetic code Many factors can influence the way that genes are expressed Nature vs. and nurture Example: conditions that affect the fetus affect adult health

Teratogens

Teratogens: Agents that cause a permanent alteration in form or function of the infant when present during critical phases of fetal development. - Alcohol, cigarettes, medications, drugs - Some infections - Radiation

Gene

The fundamental physical and functional unit of heredity. A gene is an ordered sequence of nucleotides located in a particular position on a particular chromosome that encodes a specific functional product (i.e., a protein or RNA molecule).

Translation

The process in which the genetic code carried by mRNA directs the synthesis of proteins from amino acids.

Epigenetics

The study of heredity relating to non-DNA sequence changes

Congenital Anomalies: Birth Defects

There has been a slowly increasing rate of birth defects over the past several decades. About 3-4% of all live births are complicated by some kind of anomaly Older and younger mothers giving birth Increasing births among women with chronic diseases and gestational diabetes Assisted reproduction Exposures to mutagens?

Transcription

Things that affect transcription Transcription factors Exposes RNA polymerase binding sites

Facilitated Diffusion

Through channels or Aquapores.

Prokarotes

Unicellular No membrane bound organelles Everything dissolved in cytoplasm Have a flagellum movement Cell wall and membrane Asexual reproduction Horizontal gene transfer

Eukarotes

Unicellular or Multicelluar Have membrane bound organelles Nucleus DNA Cell membrane Asexual (mitosis) or sexual (meiosis) reproduction Genetic recombination

Allele

Variations of genes exists in the form of alleles For each gene you have two copies of each gene (1 each from biological parents) Variations of gene exists because of alternative in alleles at a specific location You are either: Heterozygote with one copy of the dominant and recessive allele Homozygote (two copies) for the major allele Homozygote for the minor allele

Lipids

Water insoluble Hyodrophobic

Phosphate

Water soluble Hydrophilic

Congenital Defect

a problem that is present (though not necessarily apparent) at birth; such defects may stem from genetic and prenatal influences or from complications of the birth process

Fetal alcohol syndrome

abnormal facial features; intra-uterine growth retardation (IUGR); problems with learning, memory, attention span, problem-solving, speech, and hearing

Congenital Anomalies

broad category that includes malformations with no known inheritable genetic cause such as club foot, genetic conditions such as cleft palate, and conditions related to teratogen exposure in the fetal period

Mendelian Disorder

caused by a single mutation in one gene

Cytosol

clear fluid portion where particles are dissolved

Mutations

create slightly different versions of the same gene Mutations ≠ bad Mutations = variation Estimated that each person generates 60 new mutations that their parents don't have

Kidney cells

eliminate waste in urine (exchange of materials)

Endoplastic Reticulum (ER)

flat tubular structure

Autosomal Disorder

genetic disorder that caused by faulty allele that lies on autosomal chromosomes

ATP

is the common energy "currency" of the body Adenosine + 3 phosphate groups; When the bond is split, energy is released.

Tobacco

low birth weight (LBW), IUGR, stillbirth, infant mortality, and SIDS.

Cocaine/crack

miscarriage, LBW, preterm delivery, genitourinary abnormalities, neonatal withdrawal

Types of Mutations

missense, nonsense, intsertion, deletion

Sex-Linked (X-linked)

mutation on X chromosome - phenotype more likely to be expressed/severe in males

Autosomal Dominant

phenotype is expressed in those who inherit only one copy an autosomal gene mutation

Autosomal Recessive

phenotype is expressed in those who inherit two copies of an autosomal gene mutation at the same locus

Congenital

present since birth

Active Transport

requires carrier protein

Nerve cells

send "messages" to the brain (responding to changes in the surrounding environment)

Allostatic Load

the long-term negative impact of the stress response on the body

Single Nucleotide Polymorphism (SNP)

the most common genetic variations whose effects can range no effect to altered proteins.

Allostatic Load

the wear and tear on body which accumulates as an individual is exposed to repeated stress

co-transport

uses differences across membrane to pull other molecules with it.

Muscle cells

voluntary contraction for movement (selective intracellular movement)