genetics

Mutation

Change in DNA sequence 

Loss of Function Mutation

A genetic change that reduces or completely eliminates the activity of a gene or its protein product

Gain of Function Mutation

a genetic change that results in a gene or its protein product having increased activity, a new function, or being active at inappropriate times or place

Polymorphism

presence of multiple versions (alleles) of a gene within a population, where each allele has a frequency of at least 1% Usually does not cause disease

What's a gene variant that's NOT harmful?

 A neutral or benign gene variant is a genetic change that does not cause any detectable negative health effects.

Germline Mutation

During meiosis, Affects potential future offspring 

Somatic Mutation

 During mitosis, Affects only the individual

Genomic Mosaic

An individual whose body has two or more genetically different sets of cells due to mutations that occur after fertilization

How is the body a genomic mosaic

because it is composed of cells that can have different genetic makeups, even within the same individual

How does a mutation cause sickle cell disease?

A mutation in the HBB gene causes sickle cell disease by changing one amino acid in the hemoglobin protein, which makes red blood cells form a rigid, sickle shape that blocks blood flow and breaks down easily.

Why are mutations in collagen genes especially likely to affect health

Mutations in collagen genes are especially likely to affect health because collagen is a major structural protein in skin, bones, and connective tissues, so defects can weaken these tissues and lead to serious disorders.

Describe a pair of allelic diseases?

A pair of allelic diseases are two different disorders caused by mutations in the same gene—for example, Duchenne muscular dystrophy and Becker muscular dystrophy, both caused by mutations in the DMD gene, but differing in severity due to the type of mutation.

How can DNA spontaneously mutate?

DNA can spontaneously mutate through natural errors in replication or chemical changes that alter the genetic code.

DNA transition

a point mutation where one purine is replaced with another purine (A ↔ G) or one pyrimidine with another pyrimidine (C ↔ T).

DNA transversion

a point mutation where a purine is replaced with a pyrimidine or vice versa (A or G ↔ C or T).

Missense mutation

Nonsense mutation

a DNA change that converts an amino acid codon into a stop codon, causing early termination of the protein.

What two types of mutations occur after the reading frame?

frameshift mutations and in-frame mutations

List the four ways that DNA can mutate without affecting the phenotype?

silent mutations, mutations in non-coding regions, redundancy in the genetic code, and mutations that are neutral.

Cite two ways a transposon can disrupt gene function

inserting into coding regions, leading to loss of function mutations, or by inserting into regulatory regions, affecting gene expression patterns

What is a molecular explanation for the worsening of an inherited illness over generations?

expansion of trinucleotide repeats in certain DNA sequences

Explain how a copy number variant differs from missense mutation?

A CNV involves changes in the number of copies of a DNA segment, while a missense mutation involves a change in a single DNA base, leading to a different amino acid in the protein

How can a single-base mutation encode a protein that is missing many amino acids?

due to a nonsense mutation or a frameshift mutation

Conditional Mutation

a genetic change where an organism displays a wild-type (normal) phenotype under certain environmental conditions (permissive), but a mutant phenotype under other conditions (restrictive)

Transcription

DNA —> RNA ; the process by which a segment of DNA is copied into RNA by the enzyme RNA polymerase.

Translation

RNA → protein ; the process by which the sequence of a messenger RNA (mRNA) molecule is decoded to build a corresponding chain of amino acids, forming a protein.

True or False … Protein produces phenotype

True

Exons

Exons are the coding regions of a gene that remain in the mature mRNA after splicing and are translated into the amino acid sequence of a protein.

Introns

Introns are non-coding regions of a gene that are transcribed into pre-mRNA but are removed during splicing and not included in the final mature mRNA.

Splicing

In genetics, splicing is the process by which introns (non-coding regions) are removed from a newly synthesized pre-mRNA transcript, and exons (coding regions) are joined together to form a mature mRNA molecule ready for translation.

Amino acid in translation

During translation, amino acids are brought to the ribosome by tRNAs and linked together in the order specified by the mRNA codons to form a protein.

Anticodon

a sequence of three bases on a tRNA molecule that pairs with a complementary codon on the mRNA during translation.

genetic mosaicism  

occurs when an individual has two or more genetically distinct cell populations within their body, originating from a single fertilized egg, due to mutations that happen during development.

Proteus syndrome

a rare genetic disorder characterized by overgrowth of bones, skin, and other tissues, caused by a mosaic mutation in the AKT1 gene, which leads to abnormal cell growth in affected areas of the body.

Can Somatic mutation cause cancer

Yes ;  If the mutated genes are involved in cell cycle regulation ; Typically more than 1 mutation to cause cancer

What types of mutations have an effect on the phenotype?

Loss of function mutations as well as a gain of function mutation

Point mutation

A single nucleotide change ; deletion, insertion, deletion

Silent mutation

a change in the DNA sequence that does not alter the amino acid sequence of the resulting protein

Missense mutation

Amino acid change ; a genetic change in which a single nucleotide alteration causes one amino acid in a protein to be replaced with a different one.

Nonsense Mutation

a genetic change where a codon is altered to become a stop codon, resulting in a prematurely shortened (truncated) protein.

Frameshift mutation

In is a genetic mutation caused by the insertion or deletion of nucleotides (1 or 2bp) that shifts the reading frame of the mRNA, often leading to a completely different and usually nonfunctional protein.

Expanding repeat mutation

a genetic mutation where DNA repeats increase with each generation

Expanding repeats

Repetitive sequence ; Increases with each generation

“Anticipation”

Symptoms worse with each generation

Myotonic dystrophy

a genetic disorder caused by an expanding repeat mutation (often a CTG repeat in the DMPK gene) that leads to progressive muscle weakness, delayed relaxation of muscles (myotonia), and can also affect the heart, eyes, and endocrine system

Spontaneous mutation rate

the natural frequency at which new mutations occur in a genome without external influence ; varies per gene

Expanding repeats

The DNA goes through genetic change and an expression change.

What is the genetic change that expanding repeats go through?

DNA bind itself to hairpin loops which increase expansion

What is the expression change that expanding repeats go through?

Long mRNA binds to proteins

Palindrome sequences

located on different stands ; might pair during replication which confuse DNA polymerase. These sequences create hairpin structures.

Mutational hotspot

inverted repeats

Repeated genes

Misaligned crossing over. Include Deletions and Insertions

Mutagens

Chemicals or radiation

Name three natural mutagens

Sunlight, cosmic, radium in earths crust

UV light & Mutation

UVB light → covalent bonds between bases, especially thymine causing Thymine dimers ; DNA polymerase inserts non-complementary base

Name 6 man made mutations

X-rays, Cigarette smoke, Hair dye, Smoked meats , Food additives, Flame retardants

Nucleotide excision repair

Removes up to 30 bases ; Damage from UV light, carcinogens, oxidative damage

Excision repair ; Base excision repair

Removes 1-5 bases ; Only repairs oxidative damage

Mismatch repair

a DNA repair mechanism that corrects errors made during DNA replication, such as mispaired bases or small insertions/deletions, to maintain genetic accuracy and prevent mutations.

Repair of double-strand break

a crucial cellular process that fixes breaks in the DNA strands, often involving homologous recombination or non-homologous end joining to restore DNA integrity.

DNA repair disorders

Mutations and broken chromosomes persist ; risk of certain cancers (HNPCC, XP, AT)

Hereditary Nonpolyposis Colon Cancer 

Affects 1 in 200 people ; 3% of colon cancer cases. dominant mutations in mismatch repair proteins ; different lengths of STRs in the same person

Xeroderma PigmentosumXeroderma Pigmentosum

Autosomal recessive ; Mutations in 1 of 7 nucleotide excision repair genes ; Extreme risk of cancer ; 50% of people get cancer during adolescence