BB LEC MODULE 3: BASIC PRINCIPLES OF GENETICS

Genetics

the scientific study of heredity

Gene

a sequence of nucleotides that represents a functional unit of inheritance; a region of DNA that codes for a product, either RNA or protein

Chromosome

a highly ordered structure composed of DNA and proteins that carries the genetic material

Autosome

all chromosomes other than X and Y chromosomes (X & Y Chr make up the Chromosome 23 or sex chromosomes)

Homologous Chromosomes / Homologs

sister chromosomes, the members of a pair of chromosomes in which one is inherited from the mother and the other from the father. Homo - carry the same genetic material

Locus

the position of a gene on a chromosome

Allele

an alternative form of gene occupying the same locus. may be the result of a mutation

Mutation

a permanent heritable change in the sequence of genomic DNA

Karyotype

the chromosome constitution of an individual. It is comprised of autosomes and sex chromosomes

Karyogram

a figure showing or maps out all the paired chromosomes from a cell arrayed in a standard sequence

Diploid

the presence of two copies of each unique chromosome per cell

Haploid

one copy of each unique chromosome. Half of the diploid copy of the number of chromosomes per cell

Homozygous

both alleles at a locus are the same

Heterozygous

the two alleles at a locus are different

Hemizygous

the presence of only one chromosome or chromosome segment rather than the usual two

Genotype

the genetic constitution/material inherited by an individual or organism (what is inherited)

Phenotype

the appearance of an individual that results from the interaction of environment and genotype. Traits expressed from a genotypic material inherited (what is seen)

Dominant Allele

the appearance of an individual that results from the interaction of environment and genotype. It is always expressed and alpha allele/trait

Recessive Allele

an allele that is only expressed when homozygous (containing two recessive alleles). When paired with a dominant allele (heterozygous → one recessive & one dominant), it is not expressed because only the dominant allele will be expressed.

Codominant Allele

alleles that show no dominance or recessivity to each other but, when present together, are both fully expressed

Independent Assortment

random assortment of chromosomes in the gametes; 50:50 chance of inheriting a given chromosome from one parent

Linkage

the presence of two or more genes on the same chromosome that tend to be inherited together

Crossing Over

the physical exchange of genetic material between homologous chromosomes

Recombination

the generation of new allelic combination on chromosomes, usually by crossing over

Mitosis

somatic cell division in which the DNA replicates and is evenly distributed to two equal daughter cells (equal number of duplicated chromosomes/DNA)

Meiosis

cell division in the gonads that produces the gametes (sex cells)

Nondisjunction

failure of chromosomes or chromatids to separate to opposite poles in cells division

Interphase (2N)

Resting stage between cell division; during that period cells are synthesizing RNA and proteins, and chromatin is uncondensed

Prophase (4N)

First stage of mitotic cell division. Chromosomes become more visible and condense. Each chromosome has two chromatids from duplication of DNA and chromatids are linked via the centromere. The initial parent cell undergoes mitotic cell division

Metaphase (4N)

Chromosomes move toward the equator of the cell and are held in place by proteins called microtubules attached at the mitotic spindle apparatus

Anaphase (4N)

The two sister chromatids separate. Each one migrates to opposite poles of the cell, and the diameter of the cell decreases at equator

Telophase (2N)

Chromosomes are at the poles of the cell, and the cell membrane divides between the two nuclei. The cell divides, and each cell contains a pair of chromosomes (daughter cells) identical to the parent cell.

Meiosis

The process by which cell division results in four unique daughter cells with each cell carrying half the number of chromosomes of their parent cell (haploid).

gonads; sex cells or gametes

Meosis takes place in the --- and aims to produce ---

Interphase (2N), Prophase I (4N), Metaphase I 4N), Anaphase I (4N), Telophase I (2N), Metaphase II (2N), Anaphase II (N), Telophase II (N)

Stage/ Phases in Meiosis

Interphase (2N)

Resting stage between cell division; during that period cells are synthesizing RNA and proteins, and chromatin is uncondensed (scattered and fine)

Prophase I (4N)

First stage of meiotic division. Chromosomes condense. Homologous chromosomes pair to become bivalent. Chromosome crossing over occurs at this stage.

Metaphase I (4N)

Bivalent chromosomes align at the cell equator. Bivalent chromosomes contain all four of the cell's copies of each chromosome.

Anaphase I (4N)

Homologous pairs move to opposite poles of the cell. The two sister chromatids separate

Telophase I (2N)

The cell separates to become two daughter cells. The new cells are now 2N (same number of chromosomes as the parent cell).

Metaphase II (2N)

Homologues line up at the equator.

Anaphase II (N)

Homologues move to opposite poles of the cell equator

Telophase II (N)

Each cell separates into two new cells. There are now four (N) cells with a unique genetic constitution.

1 Molecular Genetics
2 Cellular Genetics
3 Population Genetics

THREE DIFFERENT LEVEL OF GENETICS

MOLECULAR GENETICS

Are structures which contains the genetic material that is passed on from the parent cell to the offspring.

histones

Composed of long linear strands of DNA tightly coiled around highly basic proteins called ----. The complex of DNA and --- is referred to as a nucleosome.

two DNA double helices

Each chromosome is composed of

chromatid

Each double helix is termed as a ----- and the two chromatids are held together by an as yet unreplicated region of DNA known as centromere or primary constriction.

o Metacentric
o Acrocentric
o Submetacentric
o Telocentric

Chromosomes are identified by the location of the centromere (the central material of the chromosome) which are:

KARYOGRAM

• A figure that maps out the different chromosomes
• 1-22 are autosomes; X and Y are the sex chromosomes (Chromosome 23).

DEOXYRIBONUCLEIC ACID (DNA)

A masterpiece of architectural evolution and is considered the backbone of heredity

four nitrogenous bases, deoxyribose and a phosphate group

A nucleic acid composed of

adenine, cytosine, guanine, and thymine

the four nitrogenous bases are:

sugar and phosphate moieties

comprise the backbone of the DNA molecule and is joined by phosphodiester linkages. Unlike what is observed in proteins with helical structure, there is a little bonding force between the bases of the same strand which allows DNA to be strong and flexible

Hydrogen Bonding and Van der Waals forces

nitrogenous bases face into each other and are stabilized by ----

basic pH.

DNA is a nucleic acid therefore, most of the proteins that interact with it have an overall --acid ofr basic pH?--

antiparallel

All DNA in human cells is in the form of two stranded duplex with one strand in one direction and its complementary strand in the opposite direction. Thus, the strands are termed as

Replication

process of copying or creating a replica of DNA

Prophase

the stage wherein the number of DNA is replicated

bidirectional manner

Nearly all DNA replication is done in a --- and is semi-conservative in nature. Specifically, as enzymes involved in the replication process open, the double stranded DNA helix, one strand of DNA is copied in a 5 prime (5') to 3 prime (3') manner, while the other strand is open partially in sections and is copied in a 5' to 3' manner.

DNA repair systems

These mechanisms can detect the mistakes or changes and correct the actual DNA sequence thus, there is what we call ---

Photoreactivation

Becomes active and enzymatically cleaves thymine dimers when formed after exposure to UV light

Excision Repair

• a.k.a Cut and patch repair
• excision = excise = cut. The portions (a certain mistake of the DNA replication process)
that are cut are connected or patched up
• A complex process in which the disrupted region of the DNA is removed

Recombinational Repair

Uses the correct strand of DNA to fill in the strand where the error was deleted

Mismatch Repair

• Remove the incorrect nucleotides and insert the correct ones • Methyl groups on adenines are used to determine which is correct and which is a mistake

SOS Repair

Induced when DNA and cell damage occur

MUTATION

• Any change in the structure or sequence of DNA, whether it is physical or biochemical, caused by mutagens
• Although many effective DNA proofreading and repair systems help keep newly synthesized DNA from having mutations, none of these systems are fool-proof and occasional mutations occur
• Once a mutation is introduced into a DNA coding strand, the information in that strand is now altered

Point Mutation

• Simplest type of mutation
• Only one nucleotide in the dna sequence is changed

Substitution

UNDER POINT MUTATION

One nucleotide is changed to another nucleotide. Ex. thymine is changed into guanine, etc

Insertion

UNDER POINT MUTATION

An extra nucleotide is inserted into the DNA replica

Deletion

UNDER POINT MUTATION

One nucleotide is removed from the sequence

Transition

One purine is substituted for another purine, or one pyrimidine is substituted for another pyrimidine

Transversion

When a purine is substituted for a pyrimidine or a pyrimidine for a purine

Missense Point Mutation

• A result from a change in a codon, which alters the amino acid in the corresponding peptide
• There is an alteration of the base pair resulting in a different type of inherited genetic material
• E.g. Alterations in the hemoglobin molecule at a single base pair, resulting in different types of inherited anemias

Nonsense Mutation

A point change in one of the nucleotides of a DNA sequence causes one of the three possible stop codons to be formed

Frameshift Mutation

There is an insertion or deletion of one or more (but never multiplicities of three) nucleotides in the DNA sequence

RIBONUCLEIC ACID (RNA)

Occurs most often as a single-stranded structure

Uracil

RNA Differs from DNA because in place of thymine in DNA there is ----

sugar ribose

RNA Contains a --- in the backbone structure, which has the hydroxyl group at carbon 2 position

RNA

• Transmits genetic information (stored as DNA) from the nucleus to the cytoplasm
• Undergoes transcription and translation

interphase or the resting state

RNA synthesis happens or occurs during ---

Ribosomal RNA (rRNA)

• Makes up a large part of the ribosomal structure on the endoplasmic reticulum in the cytoplasm
• The site where RNA is translated into peptide
• Most abundant and consistent form of RNA in the cell

Messenger RNA (mRNA)

• The form that is transcribed from DNA
• Undergoes postsynthesis processing before it can be transferred out of the nucleus and translated
• Translation happens in the cytoplasm

Transfer RNA (tRNA)

Involved in bringing amino acids to the mRNA bound on the ribosome for protein synthesis

To create identical daughter cells containing the same number or copy of chromosomes from that of the parent cell

Goal of Mitosis

Meiosis

• The process by which cells divide that results in four unique daughter cells
o Unique because these daughter cells actually contain haploid of the number of chromosomes from the parent cell or half the number
• This only occurs or happens to produce gametes or sex cells (this happens to the gonads)

Population Genetics

This tackles on the different laws of inheritance

MENDEL'S LAW OF INHERITANCE

• Very popular
• A scientific theory of how hereditary characteristics are passed from parent organism to their offspring

1 Law of Dominance
2 Law of Independent Segregation
3 Law of Independent Assortment

Law of Dominance

When an organism has two different alleles for a trait, one allele dominates

Dominant Allele

UNDER LAW OF DOMINANCE

o Represented by a capital letter (T → tall)
o The allele that is expressed

Recessive Allele

UNDER LAW OF DOMINANCE

o Represented by a small letter (t → short)
o the only time that it becomes expressed is when a particular chromosome is homozygous (two recessive alleles)
o But if a recessive allele is paired up with a dominant allele, it is not expressed because the dominant allele is the one being expressed

LAW OF INDEPENDENT SEGREGATION

The two coexisting alleles of an individual for each trait segregate during gamete formation so that each gamete gets only one of the two alleles or haploid

LAW OF INDEPENDENT ASSORTMENT

The genes for different traits are inherited separately from each other, allowing for all possible combinations of gene to occur in the offspring

HARDY-WEINBERG PRINCIPLE

• A mathematical formula that allowed the study of Mendelian inheritance in great detail
• Formula: p2 +pq+q2

1 The population must be large
2 Mating among all individuals must be random
3 Mutations must not occur in parents or offspring
4 There must be no migration, differential fertility or mortality of genotypes studied

CRITERIA FOR USE: Hardy-Weinberg Principle

INHERITANCE PATTERN

• Autosomal Dominant
• X-Linked Dominant
• Autosomal Recessive
• X-Linked Recessive

AUTOSOMAL DOMINANT

The expression of the gene is found whenever it is inherited and occurs equally in males and females.

inherited in every generation.

In autosomal dominance, the trait should be ---

1 The trait appears in every generation
2 The trait occurs with equal frequency in males and females
3 On the average, the trait is transmitted by an affected person to half of his/her children
4 Unaffected family members don't transmit the trait to their children

CRITERIA FOR USE: Autosomal Dominant

AUTOSOMAL RECESSIVE

• Expressed only in homozygotes who have received the gene from both parents
• It does not have any gender predilection