Introduction to Genetics

Before we start

You’ll be best prepared if you go back and review

• Basics of DNA structure and function
• Protein synthesis
• The cell cycle

The plan

We’re going to start this review with a short recap of meiosis because we’ll need to have that knowledge handy to fully appreciate the mechanisms of inheritance

What is genetics, anyway?

Genetics is the study of biological inheritance. It involves understanding what genes are and how they transmit information about how to “build and operate” a biological organism

Genomics is a branch of genetics that studies the characteristics of whole genomes

• Recall that a genome is an entire set of genetic information
  • For example, your genome is the total of all your genes. The human genome is the totall of all human genes in a population (or at least all the possible genes a human could carry in a specified population).
• Genomics looks for expected locations of genes, patterns within different family groups, geographical patterns, abnormal patterns associated with disease (or disease risk) and so on
  • A very HOT area of science these days

Meiotic cell division

What is meiosis?

Meiosis is nuclear division that results in haploid (rather than diploid) daughter cells

That is, each daughter cell resulting from meiotic cell division has 23 nuclear chromosomes whereas each daughter cell resulting from mitotic division has 46 chromosomes

This occurs so that gametes (sperm or egg cells) or “germ cells” can have half the usual number of chromosomes, unite with each other, then form a single nucleus containing 46 chromosomes in the first cell of the offspring

Meiosis occurs in two steps

• Meiosis I – the “reduction division”
  • Reduces the diploid number of nuclear chromosomes to the haploid number of chromosomes
• Meiosis II – “similar to mitosis”
  • Splits the chromatids (breaks the centromeres) and separates them into two (equal-numbered) groups of single-stranded chromosomes

Meiosis I

Prophase I

• Synapsis = homologous chromosomes pair up in alignment with each other
• Crossing-over = exchange of groups of genes between homologous chromosomes (increases genetic diversity)

Metaphase I

• Homologous chromosome pairs align along metaphase plate
• Each chromosome is attached to spindle at centromere
• Independent assortment = the chromosomes find their place independently (they do not cling together in groups) —
  • You never know which member of a homologous pair will end up facing which pole of the cell
  • Produces variations in the particular mix of individual chromosomes in the daughter cells
  • Explained below (and visible in diagrams of this section of the review)

Anaphase I

• Chromosomes are pulled to opposite poles of the cells
• Failure to pull apart is “meiotic nondisjunction”
  • Results in one daughter cell with two of a particular type of chromosome and the other daughter cell with no chromosome of that type
  • Can result in trisomy (3 homologous chromosomes) or monosomy (1 chromosome) instead of the normal pair in the offspring
    • Ex: Down syndrome (trisomy 21), Turner (XO) syndrome, Klinefelter (XXY) syndrome

Telophase I

• “Puts it all back together” as in telophase of mitosis
• Sister chromatids are still attached at the centromere (unlike telophase of mitosis)
• Daughter cells then enter Interphase II
  • No DNA replication (S phase) occurs

Meiosis II

Prophase II, Metaphase II, Anaphase II, Telophase II similar to mitosis

Inheritance

Mendel

Johann Gregor Mendel, a scientist and Augustinian monk/abbot in what is now Brno (Czech Republic) is credited with the discovery of the essential principles of inheritance

• Published his findings in 1865, but went largely unnoticed until about 1900
  • Formed the basis of a set of principles known as “Mendelian genetics”
  • Is known as the founder (father) of genetics

Later, “molecular genetics” has added details to the mechanisms of how Mendel’s principles work at the molecular (DNA, etc) level

Want to know more? Read Mendel’s Principles of Heredity

Important terms and concepts

Gene – one DNA segment (sequence of codons) that encodes for one specific structural or functional protein (or polypeptide)

Trait – biological characteristic (a “genetic trait” is determined by one or more proteins produced from the code in one or more genes)

Alleles – different forms of genes producing different versions of the same trait; for example, multiple alleles exist for the gene that determines whether the brown pigment melanin will occur in the iris of the eye

Homozygous – adjective describing a condition where a person has two copies of the same allele (version) of a gene

Heterozygous – adjective describing a condition where a person has two different alleles of a certain gene

Dominant – adjective referring to any allele whose effects are expressed (observed)

• Dominant alleles are often written as uppercase abbreviations (F = freckles)

Recessive – adjective referring to any allele whose effects are masked by another allele

• Recessive alleles are only expressed when there are no dominant [masking] alleles present; that is, only in the “homozygous recessive” condition
• Recessive alleles are often written as lowercase abbreviations (f = no freckles)

Genotype – a statement of the alleles present for a particular gene

• For example, a homozygous recessive genotype can be written “ff”

Phenotype – a statement of which trait(s) is (are) observed for a particular gene

• For example, a heterozygous genotype “Ff” would produce a phenotype of “having freckles”

Carrier – individual who has a recessive allele masked by a dominant allele is said to be a “carrier” of the recessive allele because even though that person does not express the trait, he/she can pass it on to offspring (who MAY express it, if homozygous recessive for that trait)

Law of Segregation

Homologous chromosomes (each containing genes for the same sets of traits) move [or “segregate”] to different daughter cellss during meiosis

Results in gametes (sperm or egg cells formed by meiotic division) with different sets of chromosomes, perhaps each bearing different alleles of the same gene

Law of Independent Assortment

During meiosis, each pair of homologous chromosomes positions itself independently during metaphase I

This means that one pair may have the maternal version “facing” one pole and the next pair have the maternal version “facing” the opposite pole

The orientation of which way the pairs form up during metaphase I is random

Mendelian crosses

Monohybrid cross – cross-breeding individuals with different phenotypes for a certain trait

Dihybrid cross – cross-breeding individuals with different phenotypes for two different traits

Punnett square

Eponym after English geneticist Reginald Punnett

Grid used to figure out probable results from different crosses

Shows ratios of probabilities of producing different genotypes/phenotypes in the offspring

Punnett square example.
This 16-square grid shows what offspring genotypes could result in the F2 generation from crossing two parents of the F1 generation, each heterozygous for each of two different alleles (S = short tail; B = brown coat) . The results show the probabilities for EACH birth in what is called a dihybrid cross.

Pedigree

A pedigree is a chart showing genetic characteristics & relationships among individuals in a family

Pedigree 1
Autosomal recessive trait represented in red.
“Wild type” means “noncarrier” of recessive trait.
click image to enlarge (and credits)

Pedigree 2
Autosomeal dominant trait represented in red.
click image to enlarge (and credits)

Circles are females; squares are males

Horizontal lines are marriages/sexual unions; vertical lines show parent/child relationships

Solid or differently-colored symbols show individuals who express the allele; special symbols show carriers; cross-outs may indicated deceased individuals

Roman numerals (or F₁, F₂, . . . ) sometimes show successive generations

Dominance

Complete dominance – recessive alleles are not expressed at all

Codominance – both alleles produce proteins that each express or perform a certain function; thus BOTH alleles of the trait are expressed

Multiple alleles – means more than two versions of an allele exist in the human population, even though any one individual can only have two alleles maximum

Linkage

Genes are often linked—that is, they tend to be inherited together

Can be “unlinked” during crossing-over during Prophase I of meiosis

Sex-linked inheritance

• Alleles of genes on the X chromosome may be “X-linked” meaning they stay on the X chromosome (not the Y)
  • Males have only one X (and one Y); females have two X (and no Y)
    • Males with a recessive allele on their one X chromosome will express that allele
  • Females with a recessive allele on only one X chromosome will not express that allele (but will express the allele if it is present on both X chromosomes)
• Sex-influenced genes, on the other hand, are those that are affected by sex hormones

Changes in chromosomes

Mutations – any change in the structure (code) of a gene

• Chromosomal mutations – additions, deletions to a chromosome
• Point mutations – change in one or few nucleotides in a gene sequence

Deletions – loss of part of the chromosome

Duplication – added part of a chromosome

Types of inheritance

Nuclear inheritance – involves chromosomes in the nucleus

Mitochondrial inheritance – involves chromosome in the mitochondrion

Epigenetics

Epigenetics – study of factors that are inherited along with genes but are not part of the genetic code

• Genes (really, portions of genes) may have attached chemical groups that alter their function (such as turning on or off a gene’s expression)
• These chemical “markers” can be attached (or detached) as a result of biological events in a person, such as exposure to toxins, pollutants, stress, etc.
• Because these epigenetic markers can be passed along to offspring, they may also transmit their function (regulation of a gene’s expression)

Imprinting – the name sometimes given to the process of adding epigenetic markers ( the markers may then be called “imprints” that are inherited)

• For example, temporary gene inactivation in maternal or paternal genes that cause that gene to NOT be expressed  during a particular generation
• In some cases, the chemical imprint is thought to be “erased” in cells that produce gametes for the next generation, perhaps forming new imprints for that next generation.
• Example—Huntington Disease (HD) inheritance
  • 90% of HD patients inherit the HD imprints (on the gene for a protein called huntingtin) from their father, and it shows up in mid- or late adulthood
  • 10% of HD patients instead inherit the imprint from their mother, and HD shows up early in childhood
  • So in this case it matters which parent transmits the HD imprint

This may explain many cases of

• Differences between identical twins (they acquire have different markers during development)
• Disease (or een normal traits) that cannot be predicted through normal nuclear or mitochondrial inheritance
• Different traits produced by identical genes
• Exposure to toxins (as in smoking) affected offspring raised apart from the affected biological parent