Genetics Definitons

Medical Genetics

The application of genteics to medical practice, including inheritance, mapping disease genetis, diagnosis and treatment, and genetic counseling.

Disability

Any confision of the body or mind that makes it more difficult for the person with the condition to do certain activities and interact with the world around them

Medical Model of Disability

How an individuals health concerns varies from the default state or “expected/normal”

Social Model of Disability

A mismath between a persons traits, and how society acommodates for or accepts those traits - the disability is not the problem its the environment

Aspects of Clinical Genetics

Create differerntial diagngosis, select appropriate tests, interpret the testing results, disuss the impliations of the reuslts with the patient

Genotype

the genetic constitution of an indicidual organism (what your genes do)

Phenotype

the set of observable charateristics of an individual results from the interaction of its genotype with the environment (physcially see)

Dysmorphology

the study of human conggenital malformations, particularly those affecting the anatomy of the individual

Allele

One of two or more alternative forms of a gene that arise by mutation and are found at the same place on the chromosome

Pleiotropy

a single gene or genetic variant influences two or more distinct, seemingly unrelated phenotypic traits

Epistasis

The interaction of different genes that are not alleles, in particular the supression of the effect of one such gene by another

Heterogeneity

The same disorder or phenotype can be caused by different genetic changes

Polygenic/Multifactorial

Traits that are influenced by a combination of multiple genes/alleles as well as environmental factors

Expressivity

A condition may present differently in different people

Penetrance

Some people with a genetic variant may not display symptoms

Pseudogenes

Resemble functional genes but are nonfunctional (may lack sequences needed for transription or be nonfunctional due to frameshift variants)

Aroccentric Chromosomes

Chromosome where the centromere is near the end and can undergo fusions at their centromeres

Chromatin

Comprised of DNA, RNA, and protien

Euchromatin

open for transcription

Heterochroatin

tightly wound, less gene expression

X-Inactivation

a process in female mammals where one of the two X chromosomes is randomly turned off in each cell

Proximal Deletion

a genetic change where a piece of DNA from the inner section of a chromosome, close to its center or centromere, is missing.“Classic” deletion that typically causes significant health and developmental concerns, behavioral concerns (typically have variable expressivity)

Distal Deletion

A mutation where the terminal or outer part of a chromosome breaks off and is lost. Its usually found in many healthy unaffected parents and is an example of incomplete penetrance

Gene

a unit of heredity which is transferred from a parent to an offspring and is held to determine some characterisitic of the offspring

Gene Structure

Includes a transcriptional unit, promoter region, and enhancer regions

Transcriptional Unit

contains exons, introns, RNA polymerase binding site, 3’ non coding sequence. 5’ regions are important for the regulation of translation and the 3’ includes other regulatory sequences

Central Dogma

progression from DNA, to pre-mRNA, to mRNA, to protein

DNA- what do the genes say

DNA sequence and copy number

RNA- are the genes being expressed correctly

Expression level and splicing/alternative splicing

Protein- is the functions being carried out

Enzyme assays and other proteomic work done on a research basis

Epigenetics- how the genes are regulated?

Methylation patterns, parent of origin/imprinting

Transcript

theparts/sequence of a gene that will end up being translated into a protein

Canonical transcript

Predominant/common transcript in the body

Alternative transcript

alternatively spliced RNA sequences that are less comon

Silent Mutation

a change in a DNA nucleotide sequence that alters a codon but still codes for the same amino acid

Nonsense mutation

a change in a DNA nucleotide sequence that results in a premature stop codon in the RNA

Conservative Missense Mutation

a genetic change that swaps one amino acid in a protein for a different amino acid that shares similar chemical (ex. sharing polatirity)

Non-Conservative Missence Mutation

a genetic change where a single nucleotide swap replaces an amino acid with a completely different type of amino acid (opposing polarity)

Insertion-Deletions Mutation

a type of genetic change where extra DNA bases are added or existing bases are removed from a DNA sequence

Precision Medicine

Making medical and lifestyle decisions based on a person’s genetic makeup

Histone

Basic proteins that package DNA into stuctural units called nucleosomes

Nucelosome

The basic repeating structural unit of DNA packaging in eukaryotes

LINEs and SINEs

Types of repetitive, mobile DNA sequences called retrotransposons that make up over a third of the human genome

Primary Protein Structure

Sequence of Amino Acids

Secondary Protein Structure

Local structure of amino acids arranged in a repeating pattern, formed by hydrogen bonds

Tertiary Protein Structure

3 dimensional folding, due to interactions of the different amino acid side chains

Quaternary structure

Multiple chains of amino acids/subunits interacting with eachother

Collagen

Made of a triple helix of three idential protein molecules

Dominant Negative Variants

A mechanism of disease by which a variant in one allele can interfere with the function of the normal copy

Mechanism of Disease

The genetic chance has to affefct the protein structure or function so that it cant perform its specific cellular task/role - often leads to a cascade effect that causes distruption to cellular growth/function and ultimately clinicaal concerns

Types of Mechanisms of Disease

Loss of function, Haploinsufficiency, dominant negative, gain of function

Haploinsufficiency

when one functional copy of a gene is not enough to produce sufficient protein/function

Dominant Negative

One mutated copy interferes with the functioning of the normal one

Gain of Function

One mutated copy gains a new functions that interferes with celllar functioning

Triplosensitivity

Having too much protein product is the mechansim of diesase

Domains

DNA containing conserved sequences that help regulate the expression or function of nearby genes.

Motifs

Recurring tertiary structure of a protein that make up domains

Protein Complexes

2 or more associated proteins that are a type of quartenary structure

G0

Cells are at rest, not dividing

G1

Cell increases in size, synthesis of RNA and proteins take place to prepare for replication

S phase

DNA synthesis repliates the genetic material. each chromosome now consists of 2 sister chromatids

G2 phase

Further cell growth, some DNA repair takes place, metabolic changes assemble the cytoplasmi materials necessary for Mitosis and cytokinesis

M phase

a nuclear division (Mitosis) followed by a cell division (cytokinesis)

Proto-oncogene

Promote cell growth and sruvival

Tumor Supressor Genes

Prevent uncontrolled cell growth

Mosaicism

presence of two or more cell lineages with different genotypes arising fromm a single zygot in a single individual

Euploid

containing the normal entire set of chomosomes for an organism

Diploid

having two sets of every chromosome, default state for somatic cells

Haploid

Having one set of every chromosome (default for germline cells/gametes) (one of each)

Polyploid

Having more than two sets of each chromosome (2+ copies of every chromosome)

Aneuploidy

Any cell count that is other than a complete multiple of “n”

Monosomy

Missing one copy of one chromosome

Trisomy

having an extra copy of one chromosome

Meiosis

cell division that reduces the number of chromosomes by half to produce four unique haploid gametes (sperm and egg cells) for sexual reproduction

Nondisjunction

The failuer of one or more pairs of homologous chromosomes or sister chromatids to separate normally during nuclear division, usually resulting in an abnormal distribution of chromosomes in the daughter nuclei

Uniparental Disomy

Both copies of a chromosome came from the same parent

Gonadal Mosaicism

Variants occur at a higher number in the sperm or egg cells, but not in the rest of the body (parents blood sample is negative)

Chiasma

Chromosome that crosses over

Chromosome Copy Number Variants (CNV)

a circumstance in which the number of copies of a specific segment of DNA varies among different individuals genome. Ranges significantly in size, are recurrent/hotspot areas prone to deletions and duplications- we all have benign copy number variants

Balanced Translocation

Recombination between 2 non-homologous chromosomes, occurs in .18% of people. People with balanced translocations are at risk of haing children with unbalanced translocations

Robertsonian Translocations

Results in the q arms of 2 acrocentric chromosomes joining at the centromere (the two p arms of the chromosome joines together and are lost)

Uniparental Disomy

Both copies of a chromosome come from the same parent - instead of 1 copy from egg and 1 from sperm, they both come from the sperm or both come from the egg

Heterodisomy

a child inherits both chromosome copies from the same parient, but they are different homologs

Isodisomy

A child inherits both chromosome copies from the same parient and they are the same homolog (sister chromatids)

Monosomy Rescue

inititally, only had one copy of a chromosome and the cell copies its one copy —> results in isodisomy

Trisomy Rescue

Initially had 3 copies of a chromosome, and the cell kicked one of the copies out at random —> results in isodisomy or heterodisomy

Paracentric Inversion

Inversion on the chromosome that does not include he centromere

Pericentric Inversion

Inversion on the Chromosome that includes the centromere

Exogenous agents

substances, factors, or forces that originate outside of an organism, cell, or system rather than being produced internally

Endogenous Agents

biological substances, molecules, or processes that originate from within an organism, tissue, or cell rather than from an external source

DNA Damage Response

In charge of Alert the alert, respond, and result during DNA Damage checkpoint control

Mismatch Repair

Corrects erroneous Base Pairing

Homologous Recombination Repair

Occurs at double-strand breaks or when DNA repair damage causes a gap in synthesis during DNA replication

Nucleotide Excision Repair

Uv radiation is produces by a thymine dimer, which is detected & surrounding DNA form a bubble. Enzymes then detect, and cut the damaged region out of the bubble. Finally a DNA polymerase replaces the excised DNA and a lligase seals the backbone.

Carcinogenesis

process by which normal cells transform into cancer cells

Parenchyma

functionally specilaized cells, (neoplastic cells)

Stroma Cells

Supportive cells and tissues

Malignant Tumor

the lesion can invade and destroy adjacent structures and spread to distant sites to cause death

Benign Tumor

Microscopic and gross characteristics are considered to be relatively innocent, implying that it will remain localized and is typically amenable to local surgical removal —> doesnt mean its not problematic

In situ

cancer cells have not left the site of origin