ABMGG LGG key terms

A laboratory display of an individual's chromosomes arranged in pairs by size and banding pattern, used to detect numerical and large structural abnormalities. Standard analysis typically examines 20 metaphase cells at 400-550 band resolution.

A staining method using Giemsa dye that produces light and dark bands along chromosomes, allowing identification of each chromosome and detection of structural rearrangements. Resolution is roughly 5-10 megabases per band.

A genome-wide assay that measures copy number by comparing patient DNA hybridization intensity to reference DNA, detecting deletions and duplications below karyotype resolution. It does not detect balanced rearrangements or most point variants.

A segment of DNA, typically at least 50 base pairs, present in a variable number of copies between individuals. Clinically reported CNVs are classified as pathogenic, likely pathogenic, uncertain significance, likely benign, or benign.

A technique using fluorescently labeled DNA probes that hybridize to specific chromosomal regions, enabling detection of targeted deletions, duplications, and rearrangements in interphase or metaphase cells. Common probe types include locus-specific, centromeric, and painting probes.

The presence of an abnormal number of chromosomes, such as trisomy or monosomy, resulting from nondisjunction or anaphase lag. Most autosomal aneuploidies are lethal in utero except trisomies 13, 18, and 21.

The presence of two or more genetically distinct cell populations derived from a single zygote. Detection depends on the tissue sampled and the proportion of abnormal cells, and levels may differ among tissues.

The presence of cell populations derived from two or more distinct zygotes in one individual, as occurs after allogeneic hematopoietic stem cell transplant or in tetragametic twins. Distinguished from mosaicism by its separate embryonic origins.

Inheritance of both homologs of a chromosome pair from one parent, with no contribution from the other. It can cause disease through imprinting disturbances or by unmasking a recessive allele.

Parent-of-origin-specific gene expression established by epigenetic marks, usually DNA methylation, so that only the maternal or paternal allele is active. Disruption causes disorders such as Prader-Willi and Angelman syndromes.

A laboratory test measuring DNA methylation at a specific locus, commonly by bisulfite modification or methylation-specific PCR, used to diagnose imprinting disorders. It can detect abnormal methylation regardless of the underlying mechanism.

A disorder caused by a submicroscopic deletion of contiguous genes, often mediated by unequal crossing over between low-copy repeats. Examples include 22q11.2 deletion and Williams syndromes.

Loss of a chromosomal segment containing several adjacent genes, producing a combined phenotype reflecting each deleted gene. Also called a contiguous gene syndrome when the phenotype is distinctive.

Absence of one parental allele at a locus, detected on microarray as a stretch of homozygosity. It may reflect consanguinity, uniparental disomy, or somatic deletion in tumor tissue.

A chromosomal abnormality present in placental tissue but absent in the fetus, detected on chorionic villus sampling. It can cause false-positive prenatal results and is associated with fetal growth restriction.

A maternal blood test analyzing circulating placental DNA fragments to estimate risk for common aneuploidies. It is a screening test, so positive results require diagnostic confirmation by amniocentesis or chorionic villus sampling.

A short sequence motif repeated in tandem whose length varies among individuals. Used for identity testing, chimerism monitoring, and prenatal exclusion of maternal cell contamination.

Admixture of maternal cells in a fetal or product-of-conception specimen, which can mask or mimic a fetal genotype. Laboratories assess it by comparing maternal and specimen genotypes at polymorphic markers.

An enzymatic method that amplifies a targeted DNA segment through repeated cycles of denaturation, primer annealing, and extension. It underlies most molecular assays but cannot detect variants outside the amplified region.

A dideoxy chain-termination method that determines the sequence of a single amplified DNA fragment. It remains the standard for confirming variants detected by high-throughput methods.

Massively parallel sequencing of many DNA fragments simultaneously, producing short reads aligned to a reference genome. Applications include gene panels, exome, genome, and RNA sequencing.

The average number of sequencing reads overlapping a given nucleotide. Adequate depth is required to reliably call heterozygous variants and to distinguish true variants from sequencing error.

The process of classifying a sequence change using population frequency, computational prediction, functional data, and segregation evidence. Standard categories are pathogenic, likely pathogenic, uncertain significance, likely benign, and benign.

A sequence change whose clinical relevance cannot be determined from available evidence. It should not be used to make management decisions, and periodic reclassification may occur as evidence accumulates.

The proportion of chromosomes in a population carrying a particular allele, usually obtained from large reference databases. High frequency in unaffected populations argues against pathogenicity for a rare Mendelian disorder.

Allele frequency differences among ancestral groups that can create spurious associations or mislead variant classification if the reference population is mismatched. It also affects polygenic risk score portability.

Inheritance in which one altered allele is sufficient to cause disease. Affected individuals typically have an affected parent, and each child has a 50 percent risk, though de novo cases and reduced penetrance occur.

Inheritance requiring biallelic pathogenic variants for disease expression. Carrier parents are typically unaffected, and recurrence risk is 25 percent for each pregnancy.

Inheritance of a gene on the X chromosome. Males are hemizygous and usually more severely affected, while carrier females may show variable or milder features due to X inactivation.

The epigenetic silencing of one X chromosome in each female cell, establishing dosage compensation. Skewed inactivation can cause manifesting carriers of X-linked disorders or variable expression.

The proportion of individuals carrying a pathogenic genotype who show any clinical features of the disorder. Reduced penetrance can produce apparent skipped generations in dominant pedigrees.

The range of severity or types of features among individuals with the same pathogenic genotype. It differs from reduced penetrance, in which some carriers show no features at all.

Earlier onset or greater severity of a disorder in successive generations, classically caused by expansion of a repeat sequence. Examples include myotonic dystrophy and Huntington disease.

An increase in the number of copies of a three-base repeat beyond a disease threshold, often unstable during transmission. Larger expansions generally cause earlier onset and more severe disease.

A union between related individuals, which increases the chance that offspring inherit two copies of the same ancestral allele. It raises the risk for autosomal recessive disorders and influences recurrence risk counseling.

Testing individuals or couples for recessive pathogenic variants before or during pregnancy to estimate reproductive risk. Panels are typically selected by ancestry and expanded panels are increasingly used.

A process that helps individuals understand genetic risk, make informed decisions, and adapt to a diagnosis. Core elements include risk assessment, education, informed consent, and nondirective support.

A process ensuring a patient understands the purpose, benefits, limitations, and alternatives of a genetic test before agreeing to it. It must address possible incidental findings and privacy protections.

Results unrelated to the indication for testing that may have medical importance, such as a pathogenic variant in a medically actionable gene. Policies govern whether and how such findings are returned.

The probability that a disorder will occur again in a family, based on inheritance pattern, family structure, and empirical data. It is a central output of genetic counseling.