Lecture 1.1 (Central Dogma: Genomes, genes, mutations)

Genetics

study of inherited traits and their variation and transmissions.

Genetics is the science of —. What does that mean?

hereditary; It is a precise explanation of biological structures and mechanisms that determine what is inherited and how.

Heredity

the way genes transmit biochemical, physical, and behavioral traits from parents to offspring

Traits

produced by an interaction between genes and their environment. Examples includes hairline, tendency to bald and how you clasp your hands

Certain difficult to define human characteristics might appear to be inherited if —

they affect shared family members

Genes

specific segments of DNA that serve as a functional unit of heredity by encoding a particular RNA or protein. Unit of inheritance.

Mendelian traits

predominantly caused by a single gene

Multifactorial (complex) traits)

determined by one or more genes and environmental factors

Mendelian or multifactorial- polydactyly? Hair color?

mendelian; multifactorial

Central dogma

DNA is transcribed to RNA. RNA codons are scanned by ribosomes and attract tRNAs that add amino acids. These amino acids are linked to form a polypeptide.

A protein chain grows from the — terminus to the — terminus

amino to carboxyl

Transcription

process by which DNA is copied into a single stranded RNA molecule

Translation

process by which RNA codons are scanned by ribosomes and attract tRNAs that add amino acids which link to form a polypeptide

Genome

complete set of genetic instructions characteristic of an organism. Includes both protein-encoding genes and other DNA sequences.

Genomics

field that analyzes and compares whole gnomes of different species

Genome annotation

process of marking all the genes in a genome and ascribing functions to each

Locus

site of gene within a genome.

—% of DNA is similar among humans

98.9

Approximate number of gene coding for proteins

21,000

Percentage of DNA sequence in exons

1.5%

Percentage of DNA in high copy-number repetitive elements

50%

Largest gene in human genome

DMD (duchenne’s muscular dystrophy) gene which is X-linked and is about 2.4 million bp long.

TTN gene

gene with the largest number of exons (363) and has the largest exon in the human genome (17,106 bp)

A human body contains about — cells and all cells except — contain the entire genome

50 trillion; RBCs

Most — cells within an individual contain the same genome

somatic

Different subsets of genes are — in cells of different —

expressed; tissues

Epigenetic mechanisms

heritable changes in gene expression that occur independently of DNA sequence. Allows for differentiation of distinctive cell types

Examples of epigenetic mechanisms

chromatin modifications and noncoding RNAs

Stem cells

less specialized cells that provide a reserve supply of cells. Important for tissue growth and/or regeneration

DNA structure and components

deoxyribonucleic acid. Components include phosphate, sugar, and base (A,T,C, or G)

Which base pairs pair with which? How many H-bonds in each pair?

adenine to thymine/uracil (2 h-bonds) and guanine to cytosine (3 H-bonds)

Nucleosomes

basic unit of chromosome packaging

Histones that make up nucleosomes

2 of each of the following- H2A, H2B, H3, and H4

Histone that is bound to linker DNA

H1

About — bp of DNA wraps around core histone proteins of nucleosome

147

Linker DNA

DNA which connects nucleosomes. Is variable in length.

Packaging of nucleosomes condenses DNA — -fold. Because of this, 2 m of DNA in a diploid human genome may be shortened to about — m

seven. 0.25

Higher order packaging may condense chromosomes further than just nucleosomes can, though the mechanisms are unknown. What two models are there for this though?

nucleosome supercoiling model and radial-scaffold model.

Centromeres

essential for spindle attachment during meiosis and mitosis (due to kinetochore formation). Carry passenger protein to daughter nuclei. Large stretches of tandem repeat DNA sequences

𝛂-satellite

170 bp sequence that is repeated 1,700 to 29,000 times (=300-5,000 kb of centromeric sequence). May be used as molecular probes to determine chromosome content in cells.

Telomeres

end “caps” of chromosomes. Essential for complete replication of chromosome ends and for pairing of homologous chromosomes in prophase of meiosis.

What is the tandem repetitive telomeric unit sequence (for both strands of telomere DNA)

TTAGGG and CCCTAA

Levels of genetics starting from smallest to largest

DNA→ genes→chromosomes→genomes→individuals→families→populations

Most expressed genes are found in the — region of chromatids while — regions are often not expressed

euchromatin; heterochromatin

Telomerase

protein responsible for extending telomeres. usually deactivated in most cells. often reactivated in cancer.

Individuals carry — alleles for most genes

two

Dominant allele

allele is expressed if individual carries one copy (heterozygous or homozygous)

Recessive allele

must be present on both chromosomes of a pair to be expressed (homozygous only)

Pedigrees

depict inheritance patterns between members of a family. Indicate which individuals have particular inherited traits.

(pedigree) male

square

(pedigree) female

circle

(pedigree) diseased

filled in

(pedigree) sex unspecified

diamond

(pedigree) deceased

line slashes through the individual

(pedigree) mating

lines between individuals

(pedigree) consanguineous mating (incest)

double lines between individuals

Population (biological definition)

a group of individuals that can have healthy offspring together

Population (genetic definition)

a large collection of alles, distinguished by their frequencies

Gene pool

sum of all alleles in a population

Founder effect

describes a reduction in genetic variations that results when a new colony is established by a small subset of a large original population. Accelerates genetic drift by perpetuating a subset of alleles from an original population to a new one.

Exons

expressing regions-coding regions of genes

Introns

intragenic regions- noncoding regions of genes

Allele

alternate form of single gene. Discrete units of inheritance.

Homozygous

when both alleles for a gene are the same

Heterozygous

when a gene has two different alleles

Mutation

permanent change in DNA sequence of a chromosome

Germline mutation

occur in sperm or egg and are passed on to next generation

Somatic mutation

occur spontaneously in non-sex cells after conception and are not inherited

t/f all mutations are deleterious

false, they may be positive negative or neutral

Spontaneous mutations

de novo or new mutations. Not caused by exposure to a mutagen. May be caused by errors in DNA replication of normal instability of DNA.

Mutagen

chemicals or radiation that may cause mutations in DNA

Carcinogen

any cancer causing agent. Many are mutagens.

Hot spot

regions in which mutations are more likely to occur. May be caused by short repetitive sequence or palindromes

How do short repetitive sequences result in mutations?

pairing of repeated may interfere with replication or repair enzymes

How can palindromic sequences result in mutations?

often associated with inerstions or deletions

A mutation change in a DNA sequence is — in a population ( —% of alleles) and typically affects the —

rare; less than 1%; phenotype

Polymorphism

means many forms. Change in a gene that is less rare (>1% alleles in a population) than a mutation and may not affect phenotype

Gene variant

term which may used for both mutation and polymorphism

Point/substitution mutation

refer to change of a single nucleotide in DNA

Transition mutation

changes a pyrimidine to a pyrimidine or purine to purine

Transversion mutation

changes a purine to pyrimidine or pyrimidine to purine

Silent mutation

mutation causes no change in amino acid. Due to multiple codons coding for the same amino acid. Aka synonymous mutation.

Nonsense mutation

point mutation in which a stop codon is generated (UAA, UAG, UGA)

Missense mutation

point mutation in which an amino acid is changed

Insertion or deletion mutation

mutation when 1 or more nucleotides are inserted or deleted from a DNA sequence

Frameshift mutation

occurs when an insertion or deletion alters the codon reading frame such that incorrect amino acids are incorporated into the protein. Frequently results in early stop codons.

How does a mutation in G551D CFTR cause cystic fibrosis?

it swaps a glycine amino acid for an aspartic acid which causes the protein channel it encodes to be blocked

InDels

insertion or deletion mutations. Insertion adds genetic material while deletions remove genetic material.

Deletions can be anywhere from — long to —

1 bp to an entire chromosome

Inversion

when a section of a chromosome is inverted

Translocation

break off a segment from one chromosome and attaches it to another

Lethal mutation

mutation which causes developing organism to die prematurely

Conditional mutation

produces phenotypic effects only under certain conditions.

Restrictive conditions

conditions that cause a conditional mutation to produce a phenotypic effect

Permissive conditions

conditions where a conditional mutation does not produce a phenotypic effect

Temperature sensitive mutation

conditional mutation which typically has a restrictive condition of high temperatures and a permissive condition of low temps

Loss-of-function mutation

reduces or abolishes gene activity. Most common mutation type. Usually recessive (usually one normal copy of gene is enough)

Null mutation

loss of function mutation which completely abolishes gene activity

Gain-of-function mutation

increases gene activity or makes it active in inappropriate conditions. Typically dominant

Dominant-negative mutation

mutant gene product interferes with normal product. Loss of function, but dominant.