Genetics and Non-Mendelian Inheritance Flashcards

Flashcards covering Non-Mendelian inheritance, metabolic disorders, cytogenetic techniques, triplet repeat expansions, and imprinting disorders based on lecture notes.

TRIX-U

A mnemonic for Non-Mendelian inheritance examples: TR = Triplet repeats, I = Imprinting, X = X-inactivation, U = Uniparental disomy.

Tay-Sachs disease

A lysosomal storage disease caused by hexosaminidase A deficiency, leading to GM2 ganglioside accumulation ("Tay takes Hex-A away → GM2 stays").

Glycogen storage disease types

Inherited metabolic disorders remembered by "Very Powerful Cars Move": Type Ia = Von Gierke disease, Type II = Pompe disease, Type III = Cori disease, Type V = McArdle syndrome.

Copy-number variation (CNV)

Duplication or deletion of a DNA segment $\ge 1\,kb$ ("CNV Changes the Number of Very large DNA segments").

Variable number of tandem repeats (VNTR)

A short DNA sequence repeated a variable number of times ("VNTR = Variable Number of Times Repeated").

Disorders caused by enzyme mutations (PH)

Most enzyme mutation disorders are recessive; examples include PKU (phenylalanine hydroxylase deficiency) and Homocystinuria (usually cystathionine $\beta$-synthase deficiency).

Lysosomal storage diseases

Metabolic storage disorders remembered by "Lysosomes Need Their Garbage removed": N = Niemann-Pick (Types A-C), T = Tay-Sachs, G = Gaucher.

Inborn error of metabolism

An inherited defect—usually involving an enzyme—that disrupts a metabolic pathway ("Inborn = inherited; metabolism = pathway problem").

Restriction fragment length polymorphism (RFLP)

A genetic tool that compares inherited DNA-fragment patterns, making it useful for pedigree analysis ("RFLP = Relatives' Fragment Length Patterns").

Metabolomics

Studies of small metabolic products, such as amino acids and lipids ("Metabolites → metabolomics").

Proteomics

The field of study focused on proteins ("PROteomics studies PROteins").

DNA microarray

A technology that can measure the expression of thousands of genes simultaneously ("Microarray = many genes at once").

G-banded karyotype

A cytogenetic tool that detects aneuploidies and large chromosomal abnormalities but usually misses small mutations ("Karyotype = chromosome camera").

Comparative genomic hybridization (CGH)

A genomic tool that scans the entire genome for gains and losses of DNA ("CGH Checks the whole Genome for Gains and losses").

Fluorescence in situ hybridization (FISH)

A molecular technique that uses a fluorescent probe targeted to a specific chromosome region to examine a specific suspected region ("FISH Finds a specific fluorescent Spot").

Polymerase chain reaction (PCR)

A technique that amplifies a selected DNA sequence without requiring a living cell.

Vector

A vehicle for DNA that carries the DNA insert into a host cell, where the DNA can be replicated ("Vector = vehicle for DNA").

Single-nucleotide polymorphism (SNP)

A variation at a single nucleotide position ("SNP = Single Nucleotide Position change").

Online Mendelian Inheritance in Man (OMIM)

A database specifically known for cataloging human genes and inherited disorders ("OMIM = Online Map of Inherited Mutations").

Triplet repeats

DNA sequences that normally exist in the genome without causing disease, but can disrupt gene function when they expand abnormally in coding or noncoding regions.

Expanded CAG repeats in a coding region

Expanded CAG repeats encoding polyglutamine proteins that misfold and aggregate, causing a toxic gain-of-function mutation; usually autosomal dominant and neurodegenerative.

Huntington disease

An autosomal-dominant toxic gain-of-function disorder caused by CAG-repeat expansion in the coding region of the HTT gene, causing abnormal huntingtin protein aggregation, chorea, coordination problems, and cognitive/character changes appearing in a person's $30\text{s}$ or $40\text{s}$.

Coding-region vs. Noncoding-region repeat expansions

Coding-region repeats cause abnormal protein and toxic gain of function; noncoding-region repeats cause reduced/absent protein and loss of function (more common because noncoding DNA makes up a much larger portion of chromosomes).

Fragile X Syndrome

A disorder caused by CGG repeat expansion in the $5'$ UTR of the FMR1 gene (or FMR2 gene) leading to gene silencing, loss of protein function, intellectual disability, long face, large ears, large jaw, and large testes.

Fragile X CGG repeat ranges

Normal individuals: $1\text{--}30$ CGG triplet repeats; Premutation carriers: $50\text{--}200$ repeats; Full mutation (disease display): $200\text{--}4000$ repeats.

Fragile X clinical presentation and inheritance

Full mutation affects $100\%$ of males and approximately $50\%$ of females; $30\%\text{--}50\%$ of female carriers show intellectual disability or premature ovarian failure; $20\%$ of premutation males are clinically and cytogenetically normal.

Anticipation

A phenomenon where repeat length and disease severity increase in successive generations, seen in Fragile X syndrome, Huntington disease, and Myotonic dystrophy type 1 ("Fragile Hunters anticipate Myotonic problems").

Causes of noncoding-region mutations

Mutations caused by either triplet-repeat amplification or insertion of another repeated nucleotide sequence ("Noncoding mutations either Repeat or Insert").

Noncoding autosomal repeats inheritance

Usually follows an autosomal-recessive inheritance pattern, with the exception of Myotonic dystrophy, which follows an autosomal-dominant pattern.

X-inactivation

An epigenetic silencing process occurring whenever more than one X chromosome is present, including in $47,XXY$ Klinefelter males.

Genomic imprinting

An inherited epigenetic process in which one parental allele is silenced; maternal imprinting means the maternal allele is silenced, while paternal imprinting means the paternal allele is silenced.

Prader-Willi syndrome

Disorder caused by paternal 15q11–q13 deletion (with maternal allele silenced) or maternal uniparental disomy; presented with the 6 S's: Slow (intellectual disability), Short stature, Soft (hypotonia), Starving (hyperphagia/obesity), Small hands and feet, and Sex hormones low (hypogonadism).

Angelman syndrome

Disorder caused by maternal 15q11–q13 deletion (with paternal allele silenced); characterized by intellectual disability, ataxic gait, seizures, inappropriate laughter ("happy puppet syndrome"), and speaking difficulties.

UBE3A

The Angelman gene located at 15q12 ("Ubiquitin's Angel gene").