Genetics (MCBD 1a)

Genetics

• is the study of information flow

• Studies how hereditary information passes between cells and generations

Chromosomes: 

• DNA packed with proteins 

• Before replication, just one DNA molecule 

• After replication, two sister chromatids

Gene

• A DNA sequence that produces a functional RNA

• Many RNAs specify proteins 

Allele:

A sequence variant at a particular locus

What is the Correct order:

Synthesize, Check, Condense, Deliver

Check, Synthesize, Condense, Deliver

Deliver, Check, Condense, Synthesize

Condense, Deliver, Synthesize, Check

S phase

• synthesize

• DNA replication produces sister chromatids

Checkpoints

• the cell monitors DNA integrity and replication

Condensation

DNA and proteins form compact chromosomes

Mitosis + Cytokinesis

• Deliver

• chromosomes separate, the cell divides 

Interphase

the cell grows in preparation for cell division; the chromosomes are duplicated, with the genetic material DNA copied precisely 

Mitosis

the chromosome copies are separated from each other and moved to opposite ends of the cell 

Cytokinesis

the cell divides into two daughter cells genetically identical to each other and to the parent cell 

Eukaryotic Cell Cycle

Has 4 phases

M phase

mitosis and cytokinesis

G1

growth and preparation before DNA synthesis

S-phase

DNA synthesis duplicates each chromosome 

G2

preparation after S phase and before mitosis

What is the consequence of failed cell cycle checkpoints:

Cancer

In what phase of the cell cycle is the DNA replicated: 

S-phase

What happens when cells divide

Mitosis

Stage 1 of Mitosis:

Chromosomes condense as cells enter mitosis and become visible by light microscopy 

Stage 2 of Mitosis

Each chromatid contains one long DNA molecule packaged with proteins, and the compaction helps the chromosomes segregate accurately 

Stage 3 of Mitosis

DNA replication during S phase makes two sister chromatids for each chromosome 

• Each chromatid contains one DNA double helix

Stage 4 of Mitosis

Cohesion proteins hold sister chromatids together, especially around the centromere, until separation 

Centromere

center of the sister chromatids

• There is one on each sister chromatid

Cohesin

The two chromatids come together and are held together by a protein

Prophase

• Chromatin condenses to chromosomes

• Nuclear membrane dissolves

• Centrosomes go to opposite ends 

•  Getting ready for chromosomes to line up

Metaphase

• When the chromosomes are lined up in the middle of the cell

• Spindle fibers attach to the centromere of chromosomes

Anaphase

The chromosomes are pulled apart into sister chromatids

Telophase

• The nuclear envelope reforms

• Chromosomes form into chromatin 

• The cell divides (cytokinesis)

• Undoing the prophase process

Meiosis

• Contributes to genetic variation 

• Sperm and Eggs (gametes)

• Starting cell has 46 chromosomes 23 from each parent 

• There are 46 chromosomes and 92 chromatids when replicated

• Homologous Chromosomes: one chromosome from each parent

Meiosis 1

This first division separates homologous chromosome pairs, cutting the chromosome number in half.

Prophase 1

Chromosomes condense, pair up into homologous pairs (tetrads), and undergo crossing over to exchange genetic material

Metaphase 1

Paired homologous chromosomes line up along the center (equator) of the cell.

Anaphase I

Homologous chromosome pairs are pulled apart to opposite poles; sister chromatids stay together

Telophase I & Cytokinesis

Two new nuclei form and the cell splits into two haploid daughter cells

Meiosis II

This second division is similar to mitosis and separates the sister chromatids

Prophase II

Chromosomes condense again in both new cells

Metaphase II

Individual chromosomes line up single-file along the equator of each cell

Anaphase II

Sister chromatids are pulled apart and move toward opposite poles, becoming individual chromosomes

Telophase II & Cytokinesis

Nuclear membranes reform around four distinct poles, and the cells divide

• leaving  4 daughter  cells

Law of Segregation

alleles for the same trait separate during meiosis

Law of Independent Assortment

alleles for different traits act independently during meiosis

• Form all possible combos in equal amounts

Phenotype

individuals’ physical appearance

Genotype

the individual allelic makeup

Heterozygous

genotype with 2 different alleles for a trait

Homozygous

genotype with 2 identical alleles for a trait

Prometaphase

the second stage of mitosis, occurring between prophase and metaphase, during which the nuclear envelope breaks down and the mitotic spindle attaches to the chromosomes

FISH

enable scientists to pinpoint exact location of genes on chromosomes

• useful in genetic mapping, diagnosing genetic disorders and understand chromosomal abnormalities

Fruit Flies (T.H Morgan)

showed how genes are on chromosomes

• mated male files with white eyes(mutant) with female files red eyes (wild type)

• provided the first direct evidence that a gene resides on chromosomes

Hemizygous

males having only one X chromosome

SRY

It is a gene located on the Y chromosome that acts as the master genetic switch for male biological development in humans and other mammals

X Linked recessive Pedigree

50% chance of sons being affected

50% chance of daughter being carriers

Genetic Linkage

Homologous chromosomes can exchange corresponding segments during prophase I ofmeiosis (crossing over).

• Genes that are close together tend to stay together.

• The farther apart on the same chromosome genes are, the more likely they are toseparate during recombination.

Recombinant Frequency

The progeny resulting from crossing over appear in repeatable proportions

R.F = # of recombiant progeny/Total # of progeny

Genetic Map

an ordered list of the genetic loci along a particular chromosome

Linkage Map

is a genetic map of a chromosome based on recombination frequencies

Nondisjunction

pairs of homologous chromosomes do not separate normally during meiosis

Aneuploidy

results from the fertilization of gametes in which nondisjunction occurred

Chromosomal Theory of Inheritance

A principle stating that genes are located on chromosomes, and the behavior of chromosomes during meiosis explains Mendelian inheritance patterns.

How are alleles transimitted from parent to offspring?

Alleles segregate into gametes

How can we predict probabilities for offspring?

Probability rules predict offspring genotypes

Dependent Assortment

Alleles at different genes remain associated during gamete formation, producing fewer combinations

Crossing Over

produces recombinant chromosomes, which combine DNA inherited from each parent

• contributes to genetic variation by combing DNA from two parents into a single chromosome

• Occurs in Prophase I of Meiosis

Charisma

s the physical point where two non-sister chromatids exchange genetic material

Recombinant Chromatids

Chromatids with new combinations of alleles are created

Complete Dominance

occurs when phenotypes of the heterozygote and dominant homozygote are identical

Incomplete Dominance

The phenotype of the F1 generation is somewhere in between the parental phenotypes

Codominance

two dominant alleles affect the phenotype in separate, distinguishable ways

Epistasis

a genetic phenomenon where the effect of one gene (or mutation) is masked, suppressed, or modified by one or more other genes located at different loci

• phenotypical ratio; 9;3;4

Haploid

single set of chromosomes

Diploid

two sets of chromosomes usually from each parent

Transcription

RNA polymerase makes RNA from a DNA template

RNA Processing

Eukaryotic pre-mRNA is capped, spliced, and usually given a poly(A) tail.

Translation

Ribosomes read mRNA to make a polypeptide

Glucose Utillization

• first phase

• in these conditions glucose is used first

Lag Phase

After glucose is exhausted there is a phase where growth temporarily slows

Lactose Utilization (Second Phase)

Once lactose metabolism is active bacterial growth resumes

Bacterial Genes are organized into?

Operons

Laci

• regulatory gene

• located outside the operon encodes a repressor protein that can stwich off the operon

• is active

Operator and Promoter

control the entire transcription unit

Inducible Operon

• genes are off

• Inducer

• usually involved in catabolic pathways (breaking down molecules)

• lac operon

Repressible Operon

• genes are on

• corepressor

• usually involved in anabolic pathways including synthesizing molecules

• Trp operon

TrpOperon

• Absent when protein is inactive and cannot bind to the operator

• Outcome: the operon is on and enzymes are synthesized to produce typtophan

• Present when it acts as a corepressor bindng to the repressor protein

• Outcome: the operon is off and synthesis is halted to prevent overproduction

Bacterial Regulation

Activators and repressors regulate promoters. Nucleoid proteins and DNA supercoiling also influence access

Eukaryotic Regulation

Nucleosomes, transcription factors, and enhancer–promoter contacts regulate expression. Enhancers can act nearby or far away.

Layers of Eurkaryotic Gene Regulation

• Chromatin: controls access to DNA.

• Transcription: controls which RNAs are made.

• RNA processing and stability: RNA form and lifetime.

• Translation: controls how much protein is made.

• Protein processing and targeting: form and location.

• Protein degradation: controls protein lifetime.

Control Elements

segments of noncoding DNA, serve as binding sites for transcription factors regulate transcription

Cell Specific Transcription Factors

unique sets of transcription factors determine which enhancers and promoters are activated

RNA Stability

the lifespan of mRNA determines how long it can be translated into protein

Lac Operon

An inducible operon regulating lactose metabolism in E.coli

Nuclear protein are made where?

Cytoplasm

DNA Level

Variants in the promoter or regulatory regions can alter gene expression and change how much RNA is transcribed

RNA Editing

• Post-transcriptional modification of RNA.

• Changes the nucleotide sequence without altering the underlying DNA (temporary)

Positive Gene Regulation

Gene expression activation via molecules like CRP in the presence of cAMP