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PC 705 Module 1 Genetics

Terms in this set (63)

Genotype
A composition of genes at a given locus is know as a genotype.

Example: PKU (single-gene disorder)
Phenotype
The outward appearance of an individual, which is the result of both genotype and environment, is the phenotype.

Example: modification of the environment (in this case diet) produces an outwardly normal phenotype.
Karyotype
A karyotype is an ordered display of chromosomes.
Ploidy
The actual number chromosomes present in a single cell nucleus at mitosis.

44 Autosomes and 2 sex chromosomes
haploid
Haploid cells have half the number of chromosomes (n) as diploid - i.e. a haploid cell contains only one complete set of chromosomes.

Haploid cells are a result of the process of meiosis, a type of cell division in which diploid cells divide to give rise to haploid germ cells. A haploid cell will merge with another haploid cell at fertilization.
Diploid
Diploid cells contain two complete sets (2n) of chromosomes.

Diploid cells reproduce by mitosis making daughter cells that are exact replicas.
Polyploidy
Polyploidy is a condition in which there is more than 2 sets of chromosomes.

Triploids (3N), tetraploids (4N), pentaploids (5N) etc. are polyploids.

Polyploids have defects in nearly all organs.

Most die as embryos or fetuses. Occasionally an infant survives for a few days.
Aneuploid
Cells that have extra chromosomes or chromosomes missing are aneuploid. Two types of aneuploidy are discussed below.

Monosomy refers to a condition in which there is one chromosome is missing. It is abbreviated 2N - 1. For example, monosomy X is a condition in which cells have only one X chromosome.

A trisomy has one extra chromosome and is abbreviated 2N + 1. Trisomy 21 is an example of a trisomy in which cells have an extra chromosome 21.

Monosomies and trisomies usually result from nondisjunction during meiosis but can also occur in mitosis. They are more common in meiosis 1 than meiosis 2.

Oogenesis is more likely to continue than spermatogenesis when a chromosomal abnormality occurs. As a result, 80% to 90% of aneuploid (extra chromosomes or chromosomes missing) fetuses are due to errors in meiosis I of the female.
QUESTION

A person's karyotype shows 44 autosomes and one X chromosome. What is best interpretation of this karyotype.
The karyotype is aneuploid, and the individual has only one allele for each of the genes on the X chromosomes.
Dominant gen alleles
Observable effects of alleles (number of alternative forms of the same gene or same genetic locus).
Recessive gene alleles
Hidden effects of alleles (number of alternative forms of the same gene or same genetic locus).
Characteristics of autosomal recessive inheritance
It often skips generations; children that have the trait can have parents that do not.

Heterozygotes (carriers) do NOT have the trait; People with the trait have two copies of the genes.

Both parents have to contribute gene; If both parents have the trait, all offspring has 25% risk.

Males and females are affected equally.

Inbreeding results in a greater-than-expected number of rare autosomal recessive phenotypes.
Characteristics of Autosomal Dominant inheritance
Severe dominant diseases are rare because carriers die before they get a chance to reproduce and pass on the disease to their offspring.

Heterozygotes (Aa) have the trait.

Children with the trait have at least one parent that has the trait.

Two parents with the trait can produce a child that does not have the trait.

Both males and females are affected equally.
Compare the processes and consequence of meiosis I and meiosis II in spermatogenesis and oogenesis.
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Explain how penetrance and expressivity change the expected expression of some autosomal dominant traits and disorders.
Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also expresses an associated trait.

Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype.
Explain why X-linked recessive disorders are expressed at a higher rate in males than in females.
Recessive genes on the X chromosome have different consequences in males and females. A mutated recessive gene on the X chromosome tends to have little impact in a female because there is a second, normal, copy of the gene on the other X chromosome. By contrast, a mutated recessive X-linked gene will have an impact in a male because the genes on the Y chromosome are different from those on the X chromosome, and no second copy of the gene exists. The male must therefore pass the mutated X-linked gene to all of his daughters, but does not pass it to his sons, who all receive his Y chromosome.
Differentiate the transmission of complex diseases and transmission following Mendelian patterns.
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Describe how the epigenome is related to the genome and discuss examples of epigenetic modification that may be inherited.
A genome is your genetic makeup based on DNA when you are born. In twins, for example the genomes are identical. As you begin to age, your epigenome begins to change, this is based on your environment, as well as how your DNA transfers throughout your body. This is how to identical twins look different as the two begin to age.
Differentiate trisomy and triploidy
The trisomy is chromosomal abnormality in which there is one more than the normal number of chromosomes in a cell, and the triploidy is having a chromosome number that is three times the basic or haploid number.
Down's Syndrome

Trisomy 21
low nasal bridge / epicanthal folds / protruding tongue / flat low set ears.

Congenital heart defects are common; also have reduced ability to fight respiratory infections and increased susceptibility to leukemia.

90-95% the nondisjunction occurs in the formation of the mother's egg cell; increases with maternal age.
Trisomy 13
Trisomy 13, also called Patau syndrome, is a chromosomal condition associated with severe intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia). Due to the presence of several life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of life. Only five percent to 10 percent of children with this condition live past their first year.
Trisomy 18
Trisomy 18, (Edwards syndrome) is a condition which is caused by a error in cell division, known as meiotic disjunction.

The developmental issues caused by Trisomy 18 are associated with medical complications that are more potentially life-threatening in the early months and years of life. 50% of babies who are carried to term will be stillborn, with baby boys having higher stillbirth rate than baby girls.
Trisomy 18 characteristics
Typical characteristics of Trisomy 18 include:

Heart defects:
VSD (Ventricular Septal Defect): a hole between the lower chambers
ASD (Atrial Septal Defect): a hole between the upper chambers
Coarctation of the aorta: a narrowing of the exit vessel from the heart
Kidney problems
Part of the intestinal tract is outside the stomach (omphalocele)
The esophagus doesn't connect to the stomach (esophageal artesia)
Excess amniotic fluid (polyhydramnios)
Clenched hands
Pocket of fluid on the brain (choroid plexus cysts)
Rocker bottom feet
Delayed growth
Small jaw (mycrognathia)
Small head (microcephaly)
Low-set ears
Strawberry-shaped head
Severe developmental delays
Umbilical or inguinal hernia
Cri due Chat
Caused by deletion of part of the short arm of chromosome 5.

Low birth weight / severe mental retardation / microcephaly / heart defects / typical facial appearance.
Klinefelter Syndrome
Individuals with two X chromosomes and one Y chromosome.

Male appearance but usually sterile; half develop gynecomastia.

Caused by nondisjunction of the X chromosomes in the mother. Frequency of disorder increases with maternal age.
Turner Syndrome
Single X chromosome and no X or Y chromosome. 45X chromosomes

No Y chromosome makes them all females.

Usually sterile / short stature / webbing of neck / widely spaced nipples / coarctation of the aorta / edema in feet of newborn / sparse body hair.

Inherit X chromosome from mother thus from loss of paternal X chromosome.
Explain genomic imprinting when Angelman syndrome or Prader-Willi syndrome results.
An individual normally has one active copy of an imprinted gene. Improper imprinting can result in an individual having two active copies or two inactive copies. This can lead to severe developmental abnormalities, cancer, and other problems.

Prader-Willi and Angelman syndrome are two very different disorders, but they are both linked to the same imprinted region of chromosome 15. Some of the genes in this region are silenced in the egg, and at least one gene is silenced in the sperm. So someone who inherits a defect on chromosome 15 is missing different active genes, depending on whether the chromosome came from mom or dad.
Explain multifactorial disorders and give examples of multifactorial diseases.
A multifactorial disorder is a disorder which is brought about by an interaction of genetic factors or in some instances non-genetic, environmental factors. Examples of such disorders are birth defects and diabetes mellitus.
Genetics
The study of the mechanisms of heredity and variation of inherited traits.
Genomics
The study of the function of all the Nucleotides sequences within the entire genome of the human being.
Gene
A specific set of instructions that cells use to produce a specific protein; a recipe for making protein --- gene expression is activation.

Most genes are part of DNA within the nucleus of body cells; all human cells contain 2 sets of every gene that a human possess.

A complete set of genes is called a human genome.
Germ Cells
sperm / ova - contain only one set of every human gene.

Ovan - largest human cell

Sperm - smallest
Chromosomes
Composed of DNA and are in the cell nucleus; contain segments that are genes.

They are a temporary but consistent state of condensed DNA structure formed for the purpose of cell division.
DNA
Consists of genes and chromosomes; inside of the nucleus and is 99 % of DNA of cell; other 1 % is in Mitochondria.
(4) Nucleic Acid - Bases
1. Adenine

2. Thymine

3. Guanine

4. Cytosine

Base pairs are complimentary bases on two opposite strands of DNA; paralleled to each other on helix.
Mitosis
DNA super-coils tightly into the chromosome shape when the cell undergoes Mitosis.

When cell divides it undergoes replication or duplication of itself; this is called mitosis.
Mitosis II
Mitosis occurs in a regular pattern / cell cycle; produces 2 new cells identical to each other and to the parent cell.

After division cell goes into a resting state where it performs its functions until it is time to divide again.

Cardiac / skeletal / neurons do not divide.

Requires twice as much DNA; enters S (synthesis) phase so it is twice as long when replication begins.
DNA
Contains 46 strands of DNA; 46 loosely coiled double helix structures.

Replication begins with the separation of the two strands of the helix's.
Chromosomes
Chromosomes form during meta-phase of mitosis.
Telemere
The repetitive DNA at the end of a eukaryotic chromosome's DNA molecule. It protects the organism's genes from being eroded during successive rounds of replication.

As we age ... the telemere shortens and eventually stops with time.
Centromere
A specialized condensed region of each chromosome that appears during mitosis where the chromatids are held together to form an X shape.
Meiosis does 3 things.
Provides for constant chromosomes number between generation of offspring.

Provides for random assortment between maternal and paternal chomosomes among gametes.

Relocates or shuffles genes on the chromosomes to produce recombination of genes for a unique human being.
spermatogenesis
A process of formation and maturation of sperms in "SMFT" somatic cell division-->"Mitosis" and reproductive cell division--->"Meiosis" a reduction divison.Four spermatozoa are produced from one spermatocyte where in each carries halpoid # of chromosomes.
Non-disjunction
Non-disjunction - chromosome fails to pair up during meiosis or pair up but separate prematurely or fail to separate.

Of the possible segregation errors only trisomy 21, 18, and 13 can result in a term pregnancy
Huntington Disease
Autosomal dominant - age dependent penetrance - Disease evident between 30 and 50; no carrier status (dominant gene rules).

Brain disorder - basal ganglia. 50% chance of passing gene to offspring via either sex.

Caused by mutation of gene on chromosome 4 - seen in about 1 in every 30,000 persons
Type 1 Neurofibromatosis
Autosomal dominant disorder - growth of non-cancerous tumors - skin, brain, peripheral nerves - expressivity - may have few lesions or thousands.
½ inherited and ½ cases - no family history.
Autosomal Recessive Inheritance
Requires gene copies from each parent
Each offspring will have
¼ or 25% chance to be homozygous normal
¼ or 25% chance to be homozygous abnormal
½ or 50% chance to be heterozygous carrier
Phenylketonuria (PKU)
Metabolic Disorder -affects how body breaks down protein - can destroy nervous system if not treated early in life.

Mutation of gene on chromosome 12.

Affects 1 in 15,000 births in US.
Sickle Cell Disease
Disease of beta subunit of hemoglobin of the RBC
Mutation of gene in chromosome 11
Symptoms
Affects 1 in 500 African American newborns
X Linked Inheritance
Most X linked disorders are recessive.

Each son of a woman with an X-linked recessive gene has a 50% chance of being affected - males do not have second allele to counteract - so disease occurs; more boys with disease / girls carrier.

Examples: color blindness / Hemophilia / Duchenne Muscular Dystrophy.
Hemophilia A
Bleeding disorder; Factor VIII (F8) deficiency
Mutation is in gene for F8 on X short arm; sex link recessive.

Affects about 1 in 500 males worldwide; all daughters will be carriers.
Duchenne Muscular Dystrophy
Progressive muscle weakness & wasting - skeletal and heart muscle
Mutation of DMD gene on Xp (long arm) - this gene makes dystrophin protein
Imprinting
Certain genes are inherited in an inactivated or transcriptionally silent state at one parent loci - type depends on parent transmitting gene.

Epigenomic control - does not permanently change DNA structure.

Complete hydatidiform mole: placental origin
Ovarian teratoma: not placental.
Imprinting disorders
Angelman Syndrome: Missing gene activity that normally comes from Mother on chromosome 15 has been silenced by Methel group.

Prader-Willi Syndrome: Missing gene activity comes from Father on chromosome 15 will have compulsive eating / short stature / marked obesity.
Epigenomics
Biochemical factors that alter gene expression without changing its DNA sequence.

Methylation: Adding a methyl group to DNA coding regions silences genes in the area; occurs in Prader / Angel syndromes.
Histone (chromatin) modification: looses DNA and allows them to be turned off or on; changes expression of gene; Involves changes to proteins around which the DNA helix winds - loosening the DNA and allowing a gene to be expressed
Epigenomics
MicroRNA: may turn off gene expression;
Single stranded pieces of RNA that can bind to messenger RNA, preventing protein production.
This can turn off gene expression.
This may play a role in cancer development
Autosomal Recessive Disease
Autosomal Recessive Disease would require that we have Heterozygous carriers - Mom and Dad
What is the risk of an affected person who is heterozygous for the autosomal dominant allele to pass the trait to his or her child?
50 %
Autosomal Dominant Disease
*Normal parent/affected parent.
Affected parent - all children have 50/50 chance for the disorder
47 XX
This is a trisomy girl.

47 vs 46 genes!
meiosis
Meiosis allows for a constant chromosome number between generations.

Provides for a random assortment of maternal / paternal chromosomes.

Relocates or shuffles genes on the chromosomes.

Meiosis is two cell divisions that result in a haploid number; becoming smaller ... 23 vs 26.
Mitosis
Mitosis is becoming two individual cells.
Differences between Male and Female Meiosis?
There are three main differences in meiosis between males and females. First are the cells created: males make sperm and females make ova. The second difference is where it occurs: for males it's the testicles, while for females it's the ovaries. The last difference is what determines the sex of a child. Women have two XX chromosome and men have XY. Women can only contribute X while men contribute either X or Y.
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