Molecular Biology/ Genetics

1hr... check DNA structure

Genetics

• Study of genes, heredity, and genetic variation in living organisms

• Explores how traits are passed from parents to offspring

• Examines how genetic information influences characteristics, including physical appearance and disease susceptibility

• Classical Genetics:

  • Based on laws of inheritance from Gregor Mendel (1800s)

• Modern Genetics:

  • Studies how genes pass information using molecular chemistry (1950–present)

Genetics Timeline

• 1865: Mendel’s laws of inheritance

• 1900: Rediscovery of Mendel’s work

• 1944: DNA identified as molecule behind inheritance

• 1953: Watson & Crick describe double helix structure of DNA

• 1966: Genetic code determined

• 1972: Cohen & Boyer develop recombinant DNA technology

• 1974: Belmont Report issued on use of human subjects in research

• 1977: DNA sequencing methods developed

• 1982: GenBank database established

Mitosis - Cell Division

Cell replicates chromosomes and segregates them to produce two identical nuclei, preparing for cell division

Meiosis - Cell Division

Cell division in sexually reproducing organisms that reduces chromosome number in gametes (egg and sperm)

Chromosomes

• Long linear strands of DNA packaged with histone proteins

• All cells (except gametes) have two copies of each chromosome (homologous chromosomes)

• Humans: 2 × 23 chromosomes

  • 22 autosome pairs

  • 1 sex chromosome pair

Karyotype

• Chromosomal complement of an individual

• Men: 22 autosomes + XY

• Women: 22 autosomes + XX

DNA vs RNA

Feature	DNA	RNA
Strands	Double-stranded helix	Single-stranded polynucleotide
Shape	Stable helix	Can fold into specific shapes
Location	Nucleus, chloroplast, mitochondrion	Cytoplasm, ribosomes, nucleus
Function	Stores genetic information	Copies DNA info for protein synthesis
Sugar	Deoxyribose	Ribose

Gene

• Segment of DNA that contains the instructions for making a specific protein or functional RNA

• Responsible for hereditary traits passed from parents to offspring

• Can influence physical characteristics, biochemical pathways, and disease susceptibility

• Unit of inheritance

• Located at a specific locus on a chromosome

Allele

• A variant form of a gene at a specific locus on a chromosome

• Individuals inherit two alleles for each gene, one from each parent

• Alleles can be dominant or recessive, affecting the expression of a trait

• Responsible for genetic variation in a population

Homozygote

An individual with two identical alleles for a particular gene at a specific locus

Heterozygote

An individual with two different alleles for a particular gene at a specific locus

Dominant Allele

An allele that expresses its trait even when only one copy is present (heterozygous condition)

Recessive Allele

An allele that expresses its trait only when two copies are present (homozygous condition)

Gene Clusters

• Groups of functionally related genes located close together on the same chromosome

• Positioned to allow coordinated regulation and controlled expression

Genotype

The genetic make-up of an organism that determines its traits/ phenoytype

Phenotype

The visible characteristics of an organism, resulting from the interaction of genotype and environment

The Human Genome (photo)

The Human Genome

• The nuclear genome provides the great bulk of essential genetic information, most of which specifies polypeptide synthesis on cytoplasmic ribosomes

• The mitochondrial genome specifies only a very small portion of the specific mitochondrial functions

• The bulk of the mitochondrial polypeptides are encoded by nuclear genes and are synthesized on cytoplasmic ribosomes before being imported into the mitochondria

Nuclear Genome - Human Genome

• The nucleus of a human cell typically contains more than 99% of the cellular DNA

• DNA is structured in long strands that are wrapped around protein complexes called nucleosomes that consist of proteins - histones

• Such structured DNA constitute a chromosome

• The human cell has 46 chromosomes:

  • 22 pairs of autosomes

  • 1 pair of sex chromosomes, X and Y

• Nuclear genome: 3200 Mb, ~22,000 genes

• 4.5% highly conserved including 1.5% coding DNA and 3% of conserved untranslated & regulatory sequences

• 90%-95% of the coding DNA is protein coding while the remaining (5-10%) is untranslated (RNA genes)

• The coding sequence is present in families of related sequences generated by gene duplication which resulted in pseudogenes and gene fragments

• The 95.5% non-coding DNA of the human genome is made up of tandem repeats (head to tail) or dispersed repeats resulting from retrotransposition of RNA transcripts

Mitochondrial Genome -  Human Genome

= mitochondrial DNA (mtDNA)

• Is the genetic material found within mitochondria

• It's a small circular DNA molecule distinct from the larger nuclear genome located in the cell's nucleus

• In humans, it contains 37 genes that code for proteins

• 16,569 bp

• 37 genes:

  • 13 code for enzymes of oxidative phosphorylation

  • 2 code for mt rRNAs

  • 22 code for mt tRNAs

• Copy Number and Distribution

  • A single mitochondrion contains 2 to 10 mtDNA copies

  • A single somatic cell (containing only two chromosome copies) has 100–100,000 mtDNAs

  • The number of mtDNA can vary considerably in different cell types

  • Lymphocytes have about 1000 mtDNA

  • Certain cells, such as terminally differentiated skin cells, lack any mitochondria and so have no mtDNA

• Mitochondrial DNA in Gametes

  • Sperm cells have a few hundred copies of mtDNA

  • Oocytes have about 100,000 copies, accounting for over 30% of the oocyte DNA

  • Sperm do not contribute mtDNA to the zygote (strictly maternal)

  • During mitosis, mitochondria are passed on to daughter cells by random assortment

• Mitochondrial Inheritance

  • During zygote formation, a sperm cell contributes its nuclear genome but not its mitochondrial genome to the egg cell

  • Mitochondrial genome is maternally inherited: males and females both inherit their mitochondria from their mother

  • Males do not transmit their mitochondria to subsequent generations

  • During mitotic cell division, the mtDNA molecules of the dividing cell segregate in a purely random way to the two daughter cells

Nuclear DNA vs. mtDNA (photo)

Chromosomes Structure (photo)

Identifying Chromosomes (photo)

G-bands: dark staining bands with Geimsa

Identifying Chromosomes

• Cytogenetic techniques have been used to unravel the three-dimensional organization of the genome and epigenetic features of higher-order chromatin structure

• Size of chromosomes

• Position of centromere

Chromosomal Abnormalities

• A normal human cell contains 23 pairs of chromosomes, including 22 pairs of autosomes and a pair of sex chromosomes (XX or XY)

• There are many types of chromosome abnormalities, but they can be organized into two basic groups:

  • numerical abnormalities

  • structural abnormalities

Numerical Abnormalities - chromosome

• When an individual is missing one of the chromosomes from a pair, the condition is called monosomy

• When an individual has more than two chromosomes instead of a pair, the condition is called trisomy

• Examples:

  • Down syndrome (trisomy 21)

  • Edward’s syndrome (trisomy 18)

Structural Abnormalities (photo)

Deletion - Structural Abnormalities (photo)

Translocation - Structural Abnormalities (photo)

Chromosomes Organisation

• Eukaryote DNA is tightly bound to small proteins (histones) that package the DNA in the nucleus

• The total extended length of human DNA is nearly 2 meters, but it must fit into a nucleus with a diameter of 5 to 10 μm

• Chromatin is a complex of eukaryotic DNA and proteins

DNA to chromosome (photo)

Histones

• proteins that package and order DNA into nucleosomes to form chromatin

• Small: 10–20 kDa

• Highly conserved

• Very basic proteins

• Heavily acetylated/methylated

• A core of 8 histones (2 each of H2A, H2B, H3, and H4) around which the DNA is wrapped

• Histone H1 attached to linker DNA between nucleosomes

• Do not dissociate from DNA during DNA replication

Histones (photo)

Conformational transition b/n euchromatin & heterochromatin (photo)

Euchromatin

• The fraction of the nuclear genome which contains transcriptionally active DNA and which adopts a relatively extended conformation

• Enriched in genes

• Often under active transcription

Heterochromatin

• A chromosomal region that remains highly condensed throughout the cell cycle and shows little or no evidence of active gene expression

• Constitutive: always inactive and condensed (e.g. centromere)

• Facultative: can exist as either condensed or dispersed (e.g. mammalian X-chromosome)

Euchromatin vs. Heterochromatin (photo)

Centromere

• Constriction in the chromosome

• Region where the sister chromatids are held together

• Essential for attachment to the spindle and segregation

• A specific DNA sequence which is highly repetitive

• Centromeres are DNA sequences to which proteins bind, forming a kinetochore

Centromere (photo)

spindle fibres centre

Telomere

• Sequences at the ends of chromosomes required for replication of linear DNA

• Repetitive DNA sequence

• Protect the ends of chromosomes and prevent loss during DNA replication

• Maintain structural integrity of chromosomes

• Linked to ageing

• Bind a protein complex (shelterin) that protects the chromosome termini from degradation

Telomere (photo) 

Nucleotides

Linkage Disequilibrium

• Unlinked genes are genes located on different chromosomes or far apart on the same chromosome

• Unlinked genes are inherited independently of each other

Linkage Group

• A set of genes and their alleles located at different loci on the same chromosome

• Linked alleles tend to be inherited together

• Independent inheritance occurs only when crossing over happens

Penetrance

Measures the proportion of individuals in a population who carry a specific gene and express the associated trait

Mosaicism

• A condition in which cells within the same individual have different genetic makeups

• Can affect any cell type, including blood cells

Gene

A segment of DNA that is expressed to produce a functional product, such as rRNA, tRNA, or a polypeptide

Structure of Eukaryotic Genes

• Eukaryotic genes contain both coding and noncoding DNA

• Noncoding sequences occur both within genes and between genes

• Exons and introns

  • Coding regions called exons are interrupted by noncoding regions called introns

  • The entire gene is transcribed into RNA

  • Introns are removed by RNA splicing

  • Only exons remain in the mature mRNA

• Untranslated regions (UTRs)

  • Exons include regions at both ends of the mRNA

  • 5′ untranslated region 5′ UTR

  • 3′ untranslated region 3′ UTR

  • UTRs are not translated into protein

• Size and structure of human genes

  • Introns can be much longer than exons

  • The average human gene contains about 10 exons

  • The average human gene spans approximately 56,000 base pairs 56 kb

  • DNA composition

    • Total exon sequence about 4,300 base pairs

    • Protein coding sequence about 1,700 base pairs

    • Intron sequence about 52,000 base pairs

  • Introns make up more than 90 percent of the average human gene

Gene Structure (photo)

Distal Regulatory Element Structure (photo)

Locus Control Region

Regulatory Elements Involved in Gene Transcription

• Distal regulatory elements

• Locus control region LCR

• Insulator

• Enhancer

• Silencer

• Proximal promoter elements

  • GC rich box

  • CAAT box

• Core promoter

  • TATA box

• Transcription start site TSS

Distal regulatory elements

• Located far from the core promoter

• Contain multiple transcription factor binding sites

• Can function as enhancers to activate transcription

• Can function as silencers to repress transcription

Locus control region LCR

• Long range DNA regulatory element

• Ensures correct tissue specific expression

• Regulates a cluster of linked genes

• Functions by altering chromatin accessibility

Insulator

• DNA sequence that acts as a boundary or barrier

• Controls gene expression by blocking the influence of enhancers or silencers

• Prevents inappropriate activation or repression of neighboring genes

Enhancer

• Regulatory DNA sequence that binds transcription factors

• Increases the rate of transcription of a gene

• Can act at a distance from the target gene

Silencer

• Regulatory DNA element that reduces transcription

• Acts on its target promoter

• Repressive counterpart of enhancers

Proximal promoter elements

• DNA sequences located close to the transcription start site

• Usually within about 200 base pairs of the gene

• Bind transcription factors to regulate transcription

• Recruit RNA polymerase

• Influence how frequently a gene is transcribed into RNA

GC rich box - Proximal promoter elements

• Short regulatory DNA sequence rich in guanine and cytosine

• Binds specific transcription factors

• Enhances gene transcription

CAAT box - Proximal promoter elements

• DNA promoter sequence recognized by transcription factors

• Stabilizes the transcription initiation complex

• Facilitates gene expression

Core promoter

• Minimal DNA region required for transcription initiation

• Binding site for RNA polymerase and general transcription factors

• Essential for the start of gene expression

TATA box - Core promoter

• DNA promoter sequence with the consensus sequence TATAAA

• Binds the TATA binding protein

• Required for initiation of transcription

Transcription start site TSS

• Specific location on the DNA where transcription begins

• Marks the first nucleotide of the RNA transcript

• Defines the start of the gene to be transcribed

Sense and Antisense DNA Strands

• Sense strand

  • Also called the coding strand

  • Its sequence determines the protein sequence

  • Has the same sequence as the mRNA except thymine T is replaced by uracil U

• Antisense strand

  • Serves as the template strand for mRNA synthesis

  • Complementary to the RNA transcript

Noncoding Sequences in Eukaryotic Genomes

• Eukaryotic genomes contain many sequences that do not code for proteins

• Many are involved in gene regulation

• Some noncoding sequences contribute to chromosome structure and replication

• Understanding noncoding sequence function is essential for understanding development and behavior

• The ENCODE project analyzed 147 human cell lines to define functions of different sequence types

• Approximately 75 % of the human genome is transcribed

• This revealed that noncoding RNAs play a major role in gene regulation

Noncoding RNA (ncRNA)

• Refers to RNA molecules that do not encode proteins

• Lack of protein coding capacity does not mean lack of information or function

• ncRNAs have important regulatory and structural roles

Functional RNAs

• rRNA

  • Fundamental structural and functional component of ribosomes

• tRNA

  • Noncoding RNA that acts as an adaptor molecule during protein synthesis

• microRNA miRNA

  • Small noncoding RNA

  • Regulates gene expression at the post transcriptional level

  • Silences target messenger RNA mRNA

• snRNA

  • Short noncoding RNA

  • Essential for mRNA splicing and other RNA processing events

• Long Noncoding RNAs lncRNAs

  • RNA molecules longer than 200 nucleotides

  • Crucial regulators of gene expression at multiple biological levels

    • Epigenetic regulation

    • Transcriptional regulation

    • Post transcriptional regulation

  • Function as molecular scaffolds

  • Interact with DNA, proteins, and other RNAs

  • Control diverse cellular processes

  • Dysregulation is implicated in various diseases including cancer

Repetitive DNA in the Genome

• Coding regions can contain repetitive DNA sequences

• Most highly repetitive DNA is located outside genes

• Major categories of repetitive DNA

  • Heterochromatin

    • Long arrays of tandem repeats

    • Located in condensed chromosomal regions

    • Does not contain genes

  • Transposon repeats

    • Interspersed throughout the genome

    • Account for about 40 percent of the human genome

    • Found in extragenic regions, introns, and untranslated regions

Heterochromatin vs Euchromatin of Chromosome

• Heterochromatin (edge)

  • More condensed

  • Genes are silenced and often methylated

  • Gene poor with high AT content

  • Stains darker

• Euchromatin (mid area)

  • Less condensed

  • Transcriptionally active

  • Gene rich with higher GC content

  • Stains lighter

Satellite DNA

• Constitutive Heterochromatin that are found in:

  • Centromeres

  • Telomeres

  • Most of chromosome Y

  • Short arms of acrocentric chromosomes 13, 14, 15, 21, 22

• Highly condensed and transcriptionally silent

• Composed of long arrays of high copy number DNA sequences repeated in tandem

• Known as satellite DNA

• depending on size The Major types

  • Alpha satellite

  • Minisatellite

  • Microsatellite

Alpha Satellite DNA

• Consists of tandem repeats of a 171 base pair repeat unit

• Makes up the bulk of centromeric heterochromatin

• Present on all chromosomes

• Repeat units often contain binding sites for centromere protein CENP B

• Plays a critical role in centromere structure and function

Minisatellites

• Found as tandem arrays but mostly interspersed throughout the genome

• Occur at more than 1000 locations in the human genome

• Repeat units typically 10 to 100 base pairs

• Also known as VNTRs

• Hypervariable minisatellite DNA

  • Repeat units vary in size but share a common core sequence GGGCAGGAXG where X is any nucleotide

  • Found mainly near telomeres

  • Act as hotspots for homologous recombination

• Telomeric minisatellite DNA

  • Located at chromosome ends

  • Consist of 3 to 20 kb of tandem TTAGGG repeats

  • Essential for replication of linear chromosome ends

Microsatellites

• Mostly found as tandem repeats

• Consist of repeat units of 1 to 7 base pairs

• Interspersed throughout the genome

• Account for over 60 Mb or about 2 percent of the genome

• Dinucleotide repeats are the most common

  • CA TG about 1 per 36 kb

  • AT TA about 1 per 50 kb

  • AG TC about 1 per 125 kb

  • CG GC very rare about 1 per 10 Mb

• Mostly located in introns

• Rare in exons where they act as mutational hotspots

• Example of repeat contraction due to replication errors shown by loss of repeat units

Types of Non Coding Repeats - Repetitive DNA

• Minisatellites

  • Repeat size 10 to 50 bp

  • Repeated up to 1000 times

• Microsatellites

  • Repeat size 2 to 9 bp

  • Repeated 10 to 100 times

Applications of Minisatellites and Microsatellites

• Used as DNA markers due to high variability

• Important in

  • Forensic DNA analysis

  • Paternity testing

• Implicated in disease

  • Huntington’s disease

  • Myotonic dystrophy

Minisatellites and Microsatellites as DNA Markers

• Many repeats are hypervariable

• Number of repeat copies varies greatly between individuals

• Results in many alleles within the population

• STR and VNTR analysis widely used in genetic studies

• Higher probability of variation compared to non repeating DNA

• Variability arises mainly from replication errors

Tandem Repeat Elements - Satellite DNA

• Minisatellites

  • Also called Variable Number Tandem Repeats VNTRs

  • Repeat unit size in the hundreds of base pairs

  • Typically repeated a few to many times

• Microsatellites

  • Also called Short Tandem Repeats STRs or Simple Sequence Repeats SSRs

  • Repeat unit size of 2 to 6 base pairs

  • Can be repeated from 8 up to 20 or more times

Formation of Tandem Repeats

• Replication slippage (also called polymerase stuttering) is the main mechanism

• Occurs during DNA replication when DNA polymerase slips on the template strand

• Backward slippage

  • Newly synthesized strand loops out

  • Results in insertion of repeat units

• Forward slippage

  • Template strand loops out

  • Results in deletion of repeat units

• Thus, replication slippage can increase or decrease the number of tandem repeats, generating variability in repeat length

Mobile Genetic Elements

• DNA fragments that can move within the genome

• Flanked by short, inverted repeat sequences

Transposons (DNA Transposable Elements)

• Move using a cut-and-paste mechanism

• Enzyme involved: Transposase

• Mechanism:

  • Transposase cuts DNA to produce sticky ends

  • Transposable element is inserted at a new site

  • DNA ligase fills the gaps

  • Flanking repeat sequences are recreated at the insertion site

Retrotransposons

• Move via an RNA intermediate

• Mechanism:

  • DNA → RNA → DNA

  • Newly synthesized DNA is inserted into a new genomic location

Pseudogenes

• Nonfunctional DNA sequences resembling active genes

• Inactivated by mutations such as stop codons or frameshifts

• Historically considered “junk DNA”

• Some pseudogenes are transcribed into functional noncoding RNAs

Cell Cycle

• Ordered series of events involving cell growth and division producing two daughter cells

• Precisely timed and regulated stages of growth, DNA replication, and division

Major phases

• Interphase – cell grows and replicates DNA

• Mitotic phase – replicated DNA and cytoplasmic contents are separated; cell divides

• Cytokinesis

  • Final stage of cell division

  • Cytoplasm divides to form two daughter cells

Interphase - Cell Cycle

• G1 phase

  • Little visible change

  • Biochemically active

  • Accumulates building blocks for DNA, proteins, and energy for replication

• S phase (Synthesis)

  • DNA is semi-condensed as chromatin

  • DNA replication produces sister chromatids attached at centromere

  • Centrosome is duplicated

• G2 phase

  • Replenishes energy and synthesizes proteins for chromosome manipulation

  • Some organelles duplicated

  • Cytoskeleton dismantled to support mitotic spindle formation

  • Additional cell growth may occur

Mitotic Phase

• Prophase

  • Chromosomes condense and become visible

  • Spindle fibers emerge from centrosomes

  • Nuclear envelope breaks down

  • Nucleolus disappears

• Prometaphase

  • Chromosomes continue condensing

  • Kinetochores appear at centromeres

  • Spindle microtubules attach to kinetochores

  • Centrosomes move toward opposite poles

• Metaphase

  • Mitotic spindle fully developed, centrosomes at opposite poles

  • Chromosomes aligned at metaphase plate

  • Each sister chromatid attached to spindle fiber from opposite pole

• Anaphase

  • Cohesin proteins break down

  • Sister chromatids pulled toward opposite poles

  • Non-kinetochore spindle fibers elongate the cell

• Telophase

  • Chromosomes arrive at poles and begin decondensing

  • Nuclear envelope reforms around each chromosome set

  • Mitotic spindle breaks down

Mitosis vs Meiosis

• Mitosis

  • Single division

  • Produces two genetically identical diploid cells

  • For growth and repair

• Meiosis

  • Two rounds of division

  • Produces four genetically unique haploid gametes

  • For sexual reproduction

DNA Replication

• Process producing two identical replicas from one original DNA molecule

• Basis for biological inheritance

Semiconservative model

• Parental DNA strands separate

• Each strand serves as template for complementary daughter strand

• Ensures daughter strands are identical to parent strand

Replication fork

• Both strands replicate simultaneously

• Leading strand – synthesized continuously 5’ → 3’

• Lagging strand – synthesized discontinuously 5’ → 3’ as Okazaki fragments

Key enzymes and proteins

• Helicase – unwinds parental DNA

• SSBP (single-strand binding proteins) – stabilize single-stranded DNA

• Primase – synthesizes RNA primers

• DNA polymerase III – synthesizes new DNA 5’ → 3’

• DNA polymerase I – replaces RNA primers with DNA

• DNA ligase – joins Okazaki fragments

Replication direction

• Always occurs 5’ → 3’

• Leading strand continuous, lagging strand discontinuous

Summary of DNA Replication (photo)

Laws of Heredity and Genetic Variation (2)

Principle of Segregation

• Characteristics of an organism are determined by alleles occurring in pairs

• Allele pairs separate during gamete formation

• Alleles randomly unite at fertilization

• Example: in a 3-pair chromosome system, the two copies of each gene end up in different gametes

Principle of Independent Assortment

• During meiosis, any allele of one gene may combine with any allele of another gene

• Explains why offspring inherit combinations of traits that may differ from either parent

Genetic Variation

• Differences in phenotype among individuals of the same species or population

• Sources of genetic variation:

  • Crossing over during meiosis

  • Segregation and random fertilization

  • Independent assortment of alleles

  • Mutations

Crossing over - Genetic Variation (photo)

Segregation & random fertilisation - Genetic Variation (photo)

Independent assortment - Genetic Variation (photo)

Mutation - Genetic Variation (photo)

DNA Replication Errors

• DNA polymerase duplicates DNA with high fidelity using strict base-pairing rules and proofreading

• Replication errors occur about once per 10 million base pairs

• DNA repair systems correct >99.9% of errors

DNA Repair Mechanisms

• Direct Reversal Repair

  • Fixes DNA damage without excision

  • Examples:

    • UV-induced lesions repaired by photoreactivation

    • Alkylated bases repaired by enzymes like AGT and AlkB dioxygenases

• Base Excision Repair (BER)

  • Removes and replaces damaged bases

  • Involves DNA glycosylases such as OGG1

• Nucleotide Excision Repair (NER)

  • Repairs bulky lesions and cross-links from UV or chemicals

  • Removes damaged nucleotide fragments and synthesizes new DNA using the undamaged strand as template

• Mismatch Repair (MMR)

  • Corrects base mismatches and insertion-deletion loops missed during replication

  • Steps:

    • Recognition of mismatch

    • Degradation of error-containing strand

    • Synthesis of correct DNA

• Double-Strand Break Repair

  • Repairs DNA double-strand breaks (DSBs)

  • Two main pathways:

    • Homologous recombination (HR)

    • Non-homologous end joining (NHEJ)

Genetic Code

Set of rules translating the four-letter DNA code into the 20 amino acids that make up proteins

• Codons

  • Three-nucleotide sequences in DNA or RNA

  • Each codon corresponds to a specific amino acid or stop signal

  • 64 possible codons: 61 code for amino acids, 3 are stop signals

• Degeneracy of the code

  • Each codon specifies only one amino acid

  • Some amino acids are coded by more than one codon

• Wobble Hypothesis

  • Base pairing rules are relaxed at the third codon position

  • A single tRNA can recognize more than one codon at this position

mtDNA vs Nuclear DNA Codon Usage

• mtDNA

  • Stop codons: UAA, UAG, AGA, AGG

  • Tryptophan: UGA

  • Start codons: AUG, AUA, AUC, AUU

• Nuclear DNA

  • Stop codons: UAA, UAG, UGA

  • Tryptophan: UGG

  • Arginine: AGA, AGG

  • Start codon: AUG

Single-Gene Disorders

• Determined primarily by alleles at a single locus

• Homozygous – pair of identical alleles at a locus

• Heterozygous / Carrier – two different alleles at a locus

• Compound heterozygote – two different mutant alleles of the same gene

• Hemizygous – males with a single abnormal allele on the X chromosome, no second copy