Genetic Diseases and Mutations

Genetic Variation

The difference in DNA sequences being compared, which can arise from mutations and changes in copy number.

Mutations

Changes in DNA sequences that are a significant source of genetic variation, often caused by endogenous cell environment rather than external sources.

Single Nucleotide Variation (SNV)

Changes in a single nucleotide, with a frequency of less than 0.01; common type of genetic change in the genome.

Insertion or Deletion (Indel)

Nucleotide present or absent, leading to insertion or deletion variation; a common type of genetic variation.

Copy Number Variations (CNV)

Changes in the number of copies of a particular gene, which can result in diseases or altered phenotypes.

Selective Sweep

Positive selection for advantageous DNA leading to reduced population variation at sequences near the gene variant.

Autosomal Dominant Inheritance

Inheritance pattern where almost always heterozygous individuals are affected, with both sexes being equally affected.

Autosomal Recessive Inheritance

Inheritance pattern where two mutant alleles at a locus are inherited, affecting both sexes equally.

X-Linked Recessive Disorders

Disorders mostly affecting males, transmitted by unaffected carrier females; not passed from father to son.

Mitochondrial DNA Disorders

Disorders primarily affecting tissues with high energy requirements, maternally inherited, and can exhibit variable heteroplasmy.

Gene Regulation Change

Refers to alterations in the control of gene expression, impacting the production of gene products.

Premature Termination Codon

Occurs when a mutation leads to the formation of a stop codon earlier than expected, resulting in a non-functional or truncated protein.

Loss of Function Mutations

Mutations that result in a decrease or loss of the normal function of a gene product, leading to recessive or sometimes dominant genetic diseases.

Haploinsufficiency

Condition where having only one functional copy of a gene is insufficient for normal cellular function, causing disease.

Dominant-Negative Effects

Arise when a mutant protein interferes with the function of the normal protein, leading to disease manifestation.

Gain of Function Mutations

Mutations that confer new or enhanced functions to gene products, often leading to dominant diseases.

Unstable Expansion of Repeats

Refers to the expansion of repetitive DNA sequences, causing genetic diseases through the production of toxic proteins or RNAs.

Anticipation

Phenomenon where the severity of a genetic disorder increases with each generation due to the expansion of repetitive sequences.

DNA Forensics

Utilizing DNA analysis to identify individuals, determine relationships, and solve crimes through techniques like DNA fingerprinting and PCR.

Familial DNA Searching

Method of identifying suspects by comparing DNA profiles with close relatives, focusing on shared genetic markers for investigation.

categories of genetic variation

changes that don’t affect the DNA content and changes in the copy number

strand slippage

happens during DNA replication where an STR is inserted or deleted during DNA replication

Balanced structural variation

Same DNA content but the sequences are located in different positions

Unbalanced changes

changes the copy numbers can result in diseases or metabolism phenotypes

beneficial variation

it increases survival or increases the fitness becoming more prevalent in population

negative/ purifying selection

happening when variation leads to lower fitness

Black plague mutation study

found that people with certain mutation were more likely to survive than those without it Gene ERAP 1 and 2 have a C

HLPC expression

used to detect and fight against animal pathogens at low concentration but people don’t worry about that now so it’s not selected for

de novo mutation

new mutations in the parents and almost always come from the dad stemming from germline cells

if mom is carrier for x linked disorder, dad is unaffected, and son is affected next child

if next child is son there is 50% chance the son has it or is unaffected and if the next child is a female zero chance of having it and 50% chance of being a carrier

skewed X inactivation

favoring of silencing 1 over another cause

• inactivation of mutant X provides survival advantage to cells

• inactivation of normal X provides advantage

• random chance

pseudoautosomal regions

2 gene containing regions in common present on both X and Y or X and X chromosomes producing autosomal mutations

IBDs

segments that more closely related will have more similar regions