Meiosis is the process of cell division in sex cells that halves the number of chromosomes to produce haploid gametes (sex cells)-for reproduction

What are haploid gametes?

Sex cells

Meiosis produces...?

Meiosis produces haploid cells with different combinations of the parent genes- it is not identical!

When does meiosis begin and end in females?

Meiosis begins in the fetus and is completed with sperm fertilizing the oocyte

When does meiosis begin and end in males?

Sperm production begins at puberty and continues throughout the lifespan

Meiosis I

Meiosis I produces 2 haploid cells with 23 chromosomes each

Meiosis II

Meiosis II produces 2 copies of the haploid cells, for a total of 4 haploid cells

Apoptosis

programmed cell death

Mendel's First Law

Law of segregation-
the distribution of alleles of a gene into separate gametes during meiosis

Mendel's Second Law

For two genes on different chromosomes, the inheritance of one does not influence the chance of inheritance of the other

Criteria for Autosomal Dominant Trait

1) Males and females can be affected, and male-to-male transimission is possible
2) Males and females transmit the trait with equal frequency
3) Successive generations are affected
4) Transimission stops if a generation arises with no affected individuals

Criteria for Autosomal Recessive Trait

1) Males and females are affected
2) Affected males and females can transmit the trait
3) The trait can skip generations
4) Parents of affected individuals are heterozygous or homozygous with the trait

Autosomes

Chromosomes other than sex chromosomes. There are 22 pairs of automes in humans

Sex chromosomes

The X and Y chromosomes that are involved in sex determination

Characteristics of Mitochondrial Inheritance

1) All offspring inherit the trait
2) Both sexes affected equally
3) No transmission through a father
4) Reduced penetrance, variable expressivity
5) High rates of mutation because of lack of repair enzymes and free radicals generated by energy reactions

When to suspect Mitochondrial dysfunction?

1) There is no one identifying feature of mitochondrial disease
2) Patients can have combinations of problems whose onset may occur from before birth to late adult life

Homoplasmy

Homoplasmy is the presence of a mutation affecting all of the mitochondrial DNA (mtDNA) copies in a cell. Since there are hundreds or even thousands of mtDNA copies in every eukaryotic cell, mutations may either be present in all copies, homoplasmy, or affect only a fraction of them (heteroplasmy).

Heteroplasmy

Heteroplasmy is the presence of a mixture of more than one type of an organellar genome (mitochondrial DNA (mtDNA) or plastid DNA) within a cell or individual. Since every eukaryotic cell contains many hundreds of mitochondria with hundreds of copies of mtDNA, it is possible and indeed very frequent for mutations to affect only some of the copies, while the remaining ones are unaffected.

Effect of Heteroplasmy

1) Expressivity may vary among siblings based on the number of mitochondria with mutations passed to each
2) Severity depends on which tissues have cells with mitochondria mutations
3) Most severe mitochondrial disorders are heteroplasmy because homoplasmy may impair protein synthesis or energy production so much that embryo dies

1) The A1555G mutation is also a frequent cause of deafness in Spanish and Asian populations WITHOUT exposure to aminoglycosides
2)A nuclear modifier gene on chromosome 8 was recently identified and is thought to account for the deafness in those individuals who do not have aminoglycoside exposure

What is a modifier gene?

A modifier gene is one that masks or modified the expression of another gene. Another term for this is epistasis. A modifier gene can suppress or enhance another genetic trait.

Modifier gene for hearing loss?

DFNM1

DFNM1

1) located on 1q24
2) inherited in a dominant pattern
3) is a suppressor of DFNB26
4) Identified in a Pakistani family in 2000
5) Individuals who were homozygous for DFNB26 mutations AND who had the DFNM1 gene were hearing

Digenic inheritance

1) Digenic inheritance includes two different genes at two different locations
2) Mutations in each of the two unlinked genes are present in one individual, and the combination of the two genetic traits causes disease phenotype that is not apparent if the individual only carries one of the gene alterations

Digenic inheritance and hearing loss?

the interaction of the GJB2 (connexin 26) and GJB6 (connexin 30) genes to cause deafness is thought to represent an example of digenic inheritance

GJB6 (Connexin 30)

Encoded by the GJB6 gene located on choromosome 13q11.12, just upstream of the GJB2 (connexin 26) locus.
Mutations in any two of the four alleles from connexin 26 or connexin 30 can result in deafness.
-specific interaction is unknown
*** Digenic inheritance

Type II is classified as: middle age onset, dominant, SNHL, high freq dip, bilateral, progressive, non-syndromic hearing impairment while having only one of the chromosomal locations mentioned in Type I.

Uniparental Disomy

A very rare event in which a double dose of genetic material (a gene or a chromosome) is inherited from one parent, but none from the other

Two types of UPD

Isodisomy and Heterodisomy

Isodisomy

UPD
1) same chromosome is present in duplicate
2) occurs when failure of chromatids to separate occurs at second meiotic division

Heterodisomy

UPD
1) Two different chromosome homologs from one parent are present
2) Occurs when failure of normal disjunction occurs ate first meiotic division

UPD Mode of transimission

-Maternal or paternal
-occurs when a chromosome pair fails to divide correctly during meiosis
-several types of errors in chromosome segregation may be responsible

Gamete complementation- occurs when a disomic gamete (e.g. egg with 2 copies of a pair of chromosomes) is fertilized by a nullsomic gamete (e.g. sperm missing a chromosome from that pair)

UPD Mechanism Theory # 3

Somatic Recombination- can occur after fertilization in developing zygote/embryo causing mosaicism for cells with UPD and for normal cells

Anticipation

Anticipation is the clinical phenomenon that occurs when there is an earlier onset and/or increasing severity of a disease as the gene is transmitted from generation to generation
-Charcot-Marie-Tooth

Charcot-Marie-Tooth Disease (CMT)

The most common inherited peripheral neuropathy in the world, characterized by degeneration of peripheral nerves, resulting in distal muscle atrophy, sensory loss, and deformities of the hands and feet.
-Hearing loss occurs rarely
-cochlear and neural involvment (auditory neuorpathy)

Mosaicism

Mosaicism means there could be a situation where some of the cells have fewer than normal amount of chromosomes, while others have too many chromosomes
-it can also mean that a part/portion of the chromosome is missing

How does Mosaicism occur?

After fertilization, mitosis occurs - this is when the cell begins to divide
-- when mosaicism occurs, an error in cell division has occured

Monosomy X- Mosaic Turner Syndrome

-Caused by mosaicism
-Monosomy 45, X: having only one X chromosome in all cells
-Those with monosomy 45 X, had a more severe hearing loss and higher occurance of auricular anomalies and reoccuring OM

Multifactorial inheritance

-a trait, illness or syndrome determined by several genes and the environment
-traits inherited, learned or a combination of nature (genetics) and nurture (environment)

Heterogeneity

Several different genes result in one phenotype, e.g. deafness

Phenocopy

an environmental factor mimics a genetic condition that results in the same phenotype

Pleiotropy

One gene (or a pair of genes) causes multiple phenotypic effects on the body

Genotype

The specific genetic constitution of an organism: the allele combinations in an individual that cause a particular trait or disorder

Phenotype

The observable properties of an organism; the expression of genes in traits or symptoms

Allele

An alternate form of a gene

Locus

Place of a gene on a chromosome

Homozygous

having two identical alleles of a gene

Heterozygous

having two different alleles of a gene

Homologous

chromsomes with the same gene sequence

Hemizygous

the sex with half as many x-linked genes as the other; a human male

Penetrance

The percentage of individuals who possess a dominant gene and EXPRESS it

Variable Expressivity

Dominant genes- a genotype producing a phenotype that varies in severity among individuals

Epistasis

one gene masks or alters another's phenotype

Genetic Code

The genetic code is a set of rules, which maps DNA sequences to proteins in the living cell, and is employed in the process of protein synthesis

Transcription of DNA to RNA to protein has four major stages

1) Replication: The DNA replicates its information in a process that involves many enzymes
2) Transcription: The DNA codes for the production of messenger RNA (mRNA)
3) Processing: The mRNA is processed (essentially by splicing) and migrates from the nucleus to the cytoplasm
4) Translation: mRNA carries coded information to ribosomes. The ribosomes "read" this information and use it for protein synthesis.

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