Lecture 15 - Chromosome Structures and Genetic Mutations

Centromere

Molecule that divides chromosomes

P Arm

short arm of chromosome

Q Arm

long arm of chromosome

Metacentric Chromosome

Centromere is located in the middle of chromosome

Submetacentric Chromosome

Centromere is positioned between middle and tip

Acrocentric Chromosome

Centromere is near one end of chromosome (closest but not on)

Telocentric Chromosome

Centromere is at tip, lacking a p-arm

Banding Techniques

Methods used to identify different chromosomes in a given karyotype

G Banding (Giesma)

Banding Method used in human karyotyping

Fluorescent Situ Hybridization (FiSH)

Method locating specific DNA/RNA on a chromosome

FiSH Process

looks for complementary codes of specific DNA

Euchromatin Condensation

Actively Expressed/Less Condensed

Heterochromatin Condensation

Less Expressed/Continuously Condensed

Facultative Heterochromatin

Regions that can interconvert between euchromatin and heterochromatin (sometimes condensed)

Constitutive Heterochromatin

Always condensed chromosomal regions

CENP-A (H3)

Centromere Protein A (protein) that binds kinetochore to centromere (facilitates segregation)

Chromosome Territory

center of nucleus is early part of replication
edge of nucleus is later part of replication

Inter-Chromosomal Territory

Region between nucleus that houses proteins to facilitate protein transportation

Nondisjuction

failed chromosome/chromatid segregation

Euploidy

normal number of chromosome set (#n)

Aneuploidy

non-normal number of chromosome sets

Meiosis 1 Nondisjuction

N+1 aneuploidy

Gene Balance

change in dosage of gene expression affects gene product (changes phenotype)

Human Karyotype Trisomy

13, 18, 21

Trisomy 13

Patau syndrome

Trisomy 18

Edwards syndrome

Trisomy 21

Down syndrome

Down Syndrome Critical Region (DSCR)

region impacted by change in dosage of chromosome 21, correlated with DYRK and DSCAM

DYRK + DSCAM

genes linked with higher rates of Down Syndrome with higher dosage

Klinefelter

XXY (Male)

Jacob

XYY (Male)

Triple X

XXX (Female)

Turner

X (Female)

Chromosome Break Point

Region where DNA gets severed

Acentric Breakages

Lost Forever (no centromere for reattachment)

Microdeletions

1 or 2 gene deletion mutations on a chromosome (not impactful unless in DSCR)

Microduplications

1 or 2 gene duplication mutations on a chromosome (not impactful unless in DSCR)

Terminal Deletion

Loss of chromosome arm (q/p) due to lack of centromere

Partial Deletion Heterozygotes

1 normal chromosome + 1 terminal chromosome

Cri-du-Chat syndrome

abnormal larynx development due to partial deletion of chromosome 5 (heterozygous)

Interstitial Deletion

deletion in middle of the chromosome (common in cancer)

Unequal Crossing Over

Misalignment during crossing over, leaving partial duplication + partial deletion

Chromosomal Inversion

chromosome reattached in wrong orientation

Dicentric Fragment

broken chromosome at random parts causing loss of genetic information

Paracentric Inversion

Inversion does not include centromere

Acentric Fragment

Part of chromosome lost forever

Pericentric Inversion

inversion that does include the centromere

Inversion Heterozygote

1 normal chromosome + 1 inverted chromosome

Inversion Loop

Loop formed due to mismatched synapsis of inversion heterozygote

Paracentric Region

Region of Inversion Loop that is not impacted by loop

Pericentric Region

Region of Inversion Loop subjected to duplication and deletion due to loop

Chromosomal Translocation

Chromosome reattachment to nonhomologous chromosome (wrong chromosome)

Unbalanced Translocation

Chromosomal Translocation without reciprocal translocation

Reciprocal Balanced Translocation

Chromosomal Translocation with a reciprocal translocation (flipped places)

Robertsonian Translocation

Fusion of two acrocentric chromosomes.

What does fusion translocation leave?

Telocentric q arm with acentric p arm

Phenotypical Consequences of no mutated critical points

None (:

Mutation Frequency

- rate of mutations occurring in all genomes
- varied rates amongst species
- varied rates amongst organisms

Why are there typically low frequency rates?

DNA Proofreading + Efficiency of Nucleus/Cell

Mutation Hotspot

Higher frequency of mutations at certain genes

Silent Mutation

Codon Change but no Amino Acid Change

Missense Mutation

Change in Amino Acid

Nonsense Mutaiton

Premature Stop Codon

Transition Mutation

purine/pyrimidine replaces itself
- A/G = G/A
- C/T = T/C

Transversion Mutation

purine/pyrimidine replaces pyrimidine/purine
- A/G = C/T
- C/T = A/G

Frameshift Mutation

Change in reading frame (caused by addition/deletion of 1-2 nucleotides)

Reversal Mutation

Mutation Downstream of Frameshift to correct Frameshift