Definitions Flashcards
Major (morphologic) anomaly
Anatomic phenotype that represents as substantial departure from the reference population
Minor (morphologic) anomaly
Anatomic phenotype that is observed in less than 4% of the population that has no functional or cosmetic importance
Morphologic Variant of Normal
Anatomic phenotype found in more than 4% of the population but is still a small departure from the reference population.
Malformation
A non-progressive, congenital morphologic anomaly of a single organ or body part due to an alteration of the primary developmental program.
Abnormal developmental genes lead to abnormal tissue development
Deformation
Altered shape or position of a body part due to aberrant mechanical forces that distorts an otherwise normal structure.
May result in loss of symmetry, altered alignment, abnormal position, or distorted configuration
Can happen anytime in gestation or after birth. The earlier the occurrence the more difficult to correct or can cause permanent alteration of structural relationships.
Normal genes, normal tissue development UNTIL internal or external mechanical forces exerts influence on the anatomic phenotype
Disruption
A non-progressive, congenital morphologic anomaly due to breakdown of a body structure that had normal developmental potential.
Occur during fetal development
Multiple causes: vascular, infectious, teratogenic, mechanical
Can result in secondary malformation or sequence
Normal genes, normal tissue development until the destructive influence leads to abnormal tissue development.
Dysplasia
A morphologic anomaly arising either prenatally or postnatally from dynamic or ongoing alteration of cellular constitution, tissue organization or function within a specific organ or a specific tissue type.
Can be localized or widespread
Abnormal genes result in abnormal tissue development. This often continues postnatally.
Syndrome
A pattern of anomalies, at least one of which is morphologic, known or thought to be causally related
Multiple anomalies are caused directly and independently by the underlying etiologic abnormality (ex Trisomy 21)
Anomaly (morphologic)
An anatomic (microscopic and macroscopic) phenotype that represents a substantial departure (
Sequence
One or more secondary morphologic anomalies known or presumed to cascade from a single malformation, disruption, dysplasia, or deformation
Association
A pattern of anomalies, at least two of which are morphologic, that occur together more often than would be expected by chance, and where a causal relationship has not been identified.
Ex: VACTERL/VATER association
Acrocentric
A chromosome where the centromere is near one end. The gene coding material is usually located only on the long arm.
Includes chromosomes 13, 14, 15, 21, and 22
Allele
One of several alternative forms of a gene occupying a given locus on a chromosome
Allele drop out (ADO)
The failure, for technical reasons to detect an allele that is present in a sample
The failure to amplify an allele during a polymerase chain reaction
Allele frequency
The frequency in a population of each allele at a polymorphic locus
Alternative splicing
A mechanism by which different forms of mature mRNAs are generated from the same gene.
Different exons from a single gene are used to produce isoforms of a protein
Full Aneuploidy
Abnormal chromosome number differing from the usual diploid or haploid set by loss or addition of one or a small number of chromosomes
It can be the result of non-disjunction in:
- premeiotic mitotic division in the germline of either parent
- first or second meiotic division in either parent
- early embryonic mitotic (postzygotic) division in an affected individual
Partial Aneuploidy
Imbalance resulting from the gain or loss of part of a chromosome
Anticipation
Worsening of disease severity in successive generations.
Characteristically occurs in triplet repeat disorders where there is expansion of the triplet repeat in the maternal or paternal line
Apoptosis
Programmed cell death
Array-CGH
Microarray based comparative genomic hybridization
Autosome
A chromosome that is not an X or Y chromosome
There are 22 pairs of autosomes in humans.
BAC
A cloning vector derived from an E. coli plasmid
Can be used for cloning large DNA fragments
Band/Banding
Differential staining of a chromosome leading to distinction of chromosomal segments.
A Giemsa stained (G-banded) kayotype has 850 bands visible at prometaphase.
Birth prevalence
The number of cases of disorder/condition per number of live births
Bivalent
Describes a pair of homologous chromosomes that align and undergo synapsis and recombination. The double structure is termed a bivalent
Base pair (bp)
In DNA a purine and pyrimidine in
cDNA
DNA complimentary to, and copied from an RNA molecule
cDNA libraries of living cells represent the RNA content of those cells, and thereby represent expressed gene sequences
Centromere
The constricted region of a chromosome that includes the site of attachment to the mitotic or meiotic spindle
Epigenetics
Result in changes not through changes in the structure of DNA but rather in the control and expression of genes
Penetrance
The proportion of people with a relevant genotype (ex a mutation) who show the characteristics associated with that genetic change
- Highly penetrant conditions follow more Mendelian (single gene) genetics
- Reduced penetrant condition tend to follow multifactorial inheritance
Variable Expressivity
A genetic condition can involve a number of features but many affected people show only some of those features or may show a certain feature to differing degrees
Emphasize that a DNA test cannot predict severity
Variable expressivity also reflects that presence of other genes and environmental factors may play a role
Mosaic
A person whose body contains two or more genetically different cell lines
Mosaicism can have clinical significance in 3 situations:
- if mutant cells have a tendency to grow and take over
- if mutation arose early in embryonic development that the mutant line makes up a significant part of the body
- if mutation affects the germ line (sperm or egg cells or their progenitors)
Germ line mutations
The presence of an altered gene within an egg or sperm (germ line) that the altered gene can be passed down to subsequent generations.
In germline mutations, every cell in the affected person’s body also will have the mutation
Germline mosaicism
A person who by all clinical and genetic tests is entirely normal may produce several children with the same dominant or X-linked disease if he or she has a germ-line clone of mutant cells
-This is important to remember in the case of an apparent de novo dominant condition, there is a possibility that a parent may be a germ line mosaic. May have a group of eggs or sperm that have the same mutation.
Somatic mutation
Mutation occurs after conception.
Results in mosaicism in that some cells and tissues (the original cell and its daughter cells) will have the mutation and others will not
Polymorphism
When the sequence of a functioning gene is altered but does not necessarily cause disease
Mutation
When a change in DNA is associated with disease.
Mutations can lead to disease through many different mechanisms (ie altered gene expression, truncated protein, aberrant structure leads to altered binding, constituitive activity of the protein, haploinsufficency)
Arthrogryposis
=multiple congenital contractures
- contractures are the result of the limitation of fetal movement during development for a variety of causes including neurologic abnormalities, muscle abnormalities, connective tissue skeletal dysplasia, vascular compromise, fetal crowding, maternal illness or medication
- therefore this category has a large differential diagnosis -> need to assess for other clues on exam or other structural anomalies
Mutation
=variant or change in DNA, alteration, fault or mistake
-can be inherited or de novo
Define nonsense mutation
Mutations that introduce a premature stop codon
Define missense mutations
Mutations that replace one amino acid in the protein with another
Define synonymous mutations
Mutations that alter one codon for an amino acid into another codon for the same amino acid
Define frameshift mutation
Mutations that alter the triplet reading frame
Define dominant trait
=phenotype or trait observed in heterozygotes
Define haplo-insufficiency
=50% of the normal function of a gene is not sufficient for the organism
-heterozygotes will be clinically affected (aka the trait is dominant)
Define simplex case
=A single, isolated occurrence of an inherited condition in a family.
Could be due to:
- Genetic causes
- de novo mutation
- reduced penetrance
- non-paternity - Non-genetic causes
- ex diabetic embryopathy
Define isochromosome
An abnormal chromosome with two identical arms, either 2 short p arms or two long q arms.
-caused by transverse splitting
Define CpG islands
=areas with increased density of the dinucleotide sequence of cytosine-guanine
- p in CpG stands for that the cytosine and guanine bases are connected by a phosphodiester bond.
- they can form stretches of DNA several hundred to several thousand BPs long
- usually found at the 5’ end of genes, near promoter regions
- Generally unmethylated but the cytosine can be methylate to turn the genes on/off
What’s the difference between a skeletal dysplasia and a dysostosis?
Dysplasias refer to disorders with generalized abnormalities of the bones
Dysostoses refer to disorders that have a single or group of abnormal bones
What is the difference between partial and complete gonadal dysgenesis?
Complete gonadal dysgenesis=normal appearing external genitalia but the opposite chromosomal sex
Partial gondadal dysgensis=cases with ambiguous external genitalia
