Human Genetics Final

Genome

The complete set of DNA in an organism, including all genes and non-coding sequences

SSR

Short DNA sequences (2–6 bases) repeated in tandem; highly variable between individuals

STR

Another name for SSR; commonly used in DNA profiling

Penetrance

The proportion of individuals with a particular genotype who actually express the expected phenotype

Expressivity

The degree or intensity with which a trait is expressed in an individual

Polymorphism

A DNA sequence variation that is common in a population (≥1%)

Karyotype

An organized picture of all chromosomes in a cell, arranged by size and shape

Aneuploid

Having an abnormal number of chromosomes (not a multiple of n)

Euploid

Having the normal, correct number of chromosomes

Nondisjunction

Failure of chromosomes or sister chromatids to separate properly during meiosis or mitosis

Barr Body

An inactivated X chromosome in female cells

Monosomic

(2n-1) Missing one chromosome from a pair

Disomic

(2n) Normal two copies of a chromosome

Trisomic

(2n+1) Having an extra copy of a chromosome

Haploinsufficiency

When one functional copy of a gene is not enough to produce a normal phenotype

How does the Huntington protein cause brain damage?

The Huntington protein causes brain damage when it is mutated due to an expanded CAG repeat in the HTT gene which causes more glutamines in the protein. Mutant huntingtin protein causes brain damage by misfolding. Excessive glutamines cause the mis-shape

What is the molecular basis of Huntingtons starting at the DNA level?

Huntington’s disease is caused by a CAG trinucleotide repeat expansion in the HTT gene, which creates a mutant huntingtin protein with an abnormally long polyglutamine tract that misfolds and damages neurons

Exons

DNA sequences that code for proteins

Function of Exons

Transcribed into mRNA and spliced together to form the final mRNA that will be translated into protein

Introns

DNA sequences between exons that do not code for protein

Function of introns

Transcribed into pre-mRNA but removed during RNA splicing

SSRs

Short DNA sequences (2–6 base pairs) repeated multiple times in a row.

Function of SSRs

Highly polymorphic, used in genetic mapping, forensics, and paternity testing

Snips

Single base-pair differences in DNA between individuals

Function of Snips

Can affect gene function, used in genetic studies, ancestry, and disease risk prediction

Understand how SSRs are inherited

Inherited just like how any other alleles are inherited, can be shown in a punnet sqaure

Be able to interpret a DNA fingerprint (gel) like the one used in the paternity case.

To interpret a DNA fingerprint in a paternity case, match the child’s bands to the mother’s first, then ensure that all remaining child bands match the alleged father; any unmatched band excludes paternity

Understand the role of DNA polymerase and its requirements.

DNA polymerase synthesizes new DNA by extending a primer in the 5′→3′ direction using a DNA template, and it requires a primer, dNTPs, and proper ionic and temperature conditions to function

Denaturation - First step in a PCR reaction

the mixture is heated to a near boiling temperature to cause the two DNA strands to separate. This is called denaturation. This allows the DNA primers to bind via Chargaff's rule on either side of the region that is being copied

Annealing - second step in a PCR reaction

the temperature is lowered to allow the primers to bind at the correct place

Extension - Third step in a PCR reaction

the temperature is again adjusted to allow the DNA polymerase to copy the region starting from the end of each primer

How many times are the 3 steps of PCR repeated?

This cycle of three steps is repeated about 30-40 times resulting in an exponential increase in the number of copies of just the region between the primers. Often, one million copies are made in a few hours

Why is the temperature changed at each step in a PCR?

Each step requires different physical conditions:

High heat to separate DNA strands

Lower temperature to allow primers to bind

Moderate heat for polymerase activity

Cycling through these temperatures allows exponential amplification of the target DNA.

Understand why a Polymerase that resists high temperatures is important.

A heat-resistant DNA polymerase is important because PCR involves repeated high-temperature steps that would denature normal enzymes, and only thermostable polymerases can survive and continue DNA synthesis

Understand how ssrs are visualized on an agarose gel

SSRs are visualized by PCR amplification followed by agarose gel electrophoresis, where differences in repeat number produce DNA fragments of different sizes that appear as bands on the gel

Familiarize yourself with how the sex chromosomes are inherited

Sex chromosomes are inherited with the mother always contributing an X chromosome and the father contributing either an X or a Y, which determines the sex of the offspring

Understand how sex-linked conditions are inherited

Sex-linked conditions are inherited through genes on the sex chromosomes, most commonly as X-linked recessive traits, which affect males more often because they have only one X chromosome

What is the role of the SRY protein and where is its gene located?

The SRY protein initiates male sex determination by activating genes required for testes development, and its gene is located on the Y chromosome.

What is the reasons for X chromosome inactivation?

Because women have two X chromosomes while males only have one X chromosome, you might conclude that women produce twice as much protein from the X chromosome genes than males. But, certain proteins are harmful if they are present in larger amounts than necessary.For that reason, in every female cell, one of the two chromosomes is inactivated.

What is the mechanism for X chromosome inactivation?

One of two chromosomes is selected at random to produce an RNA chain from a gene called XIST. This RNA is not translated into protein. This RNA is called an RNAi for "interfering" RNA. This RNA binds to the X chromosome from which it was transcribed. XIST attracts several other untranslated RNAs and proteins and these form inactivation complexes. The transcription of the genes on this X is stopped. The DNA is chemically modified and becomes tightly packed up into a structure called a Barr body.

How do X and Y chromosomes pair during meiosis?

Pseudo autosomal regions pair during meiosis, x chromosome bends out so the par2 on the Y can meet

X Chromosome

Much larger than the Y chromosome

Contains hundreds to thousands of genes

Genes are involved in many essential cellular functions, not just sex determination

Present in both males and females

Y Chromosome

Much smaller

Contains relatively few genes

Most genes are involved in male sex determination and sperm production

Present only in males

When a nondisjunction event takes place in a cell, what happens to the distribution of that chromosome?

When nondisjunction occurs, the chromosome does not separate properly, so it is distributed unequally between the resulting cells.

One daughter cell (or gamete) receives both copies of the chromosome.

The other daughter cell receives no copy of that chromosome.

When sex chromosomes undergo nondisjunction, the outcomes are better than when autosomes undergo nondisjunction. Why is that

Nondisjunction events involving the sex chromosomes are not as bad as events involving autosomes because of X chromosome inactivation.

What is haploinsufficiency?

when a single functional gene copy cannot produce enough gene product to sustain normal function.

What problem is created in a 2n+1 individual?

has too much genetic information, causing imbalanced gene expression, which interferes with normal growth and function.

Why are 2n-1 individuals usually worse off?

because they are missing an entire copy of a chromosome, which causes severe gene dosage problems.

What are some reasons why the use of DNA in a courtroom can be problematic?

Since the DNA is usually mixed there is only a probability of a match found, this leads to data being misinterpreted and misrepresented

What is epigenetics?

Epigenetics is a process by which the activity of genes is raised or lowered.

How are genes regulated through epigenetics?

Methylation and SAM