Mutations and Inborn Errors of Metabolism (1C) - MCAT Biological and Biochemical Foundations of Living Systems

A single-nucleotide change at a specific DNA position. Point mutations involve a substitution, insertion, or deletion of a single nucleotide, altering the DNA sequence at one specific position.

A nucleotide change that does not alter the amino acid. Silent mutations occur due to the degeneracy of the genetic code, where multiple codons specify the same amino acid.

A nucleotide change that substitutes one amino acid for another. Missense mutations change the codon to one that codes for a different amino acid, potentially altering protein function.

A mutation that converts a codon into a premature stop codon. Nonsense mutations introduce a stop codon prematurely, leading to truncated proteins.

Insertion or deletion not in multiples of $3$ that shifts reading frame. Frameshift mutations disrupt the triplet reading frame of codons, resulting in altered amino acid sequences downstream.

Insertion or deletion in multiples of $3$ that preserves reading frame. In-frame mutations add or remove whole codons, maintaining the original reading frame and downstream sequence integrity.

Truncated, nonfunctional protein due to altered downstream sequence. Early frameshifts often introduce premature stop codons, producing shortened proteins that lack functionality.

A mutation that disrupts intron removal or exon joining in pre-mRNA. Splice-site mutations affect consensus sequences at intron-exon boundaries, impairing proper mRNA splicing.

A DNA change that alters transcription factor binding and gene expression. Promoter mutations modify regulatory regions, influencing the rate of transcription initiation and overall gene expression levels.

A mutation that reduces or abolishes normal gene product activity. Loss-of-function mutations impair gene product efficacy, often leading to recessive phenotypes in diploid organisms.

A mutation that increases activity or creates a new function. Gain-of-function mutations enhance or confer novel activities, frequently resulting in dominant phenotypes.

Autosomal recessive. Most inborn errors of metabolism follow autosomal recessive inheritance due to loss-of-function mutations in enzyme-coding genes.

Enzyme deficiency causing substrate buildup and product deficiency. Inborn errors often stem from mutations causing enzyme deficiencies, disrupting metabolic pathways with substrate accumulation and product shortage.

One functional allele is insufficient for normal phenotype. Haploinsufficiency occurs when a single copy of the gene fails to produce enough product for normal function, leading to dominant inheritance.

Mutant protein interferes with the function of the normal protein. Dominant-negative mutations produce defective proteins that inhibit wild-type counterparts, often in multimeric complexes.

The fraction of individuals with a genotype who express the phenotype. Penetrance measures the proportion of genotype carriers showing the expected phenotype, influenced by genetic and environmental factors.

Differences in severity or features among individuals with same genotype. Variable expressivity reflects how modifiers and environment cause phenotypic variation in individuals sharing the same mutation.

Maternal inheritance. Mitochondrial DNA is inherited solely from the mother, as sperm contribute negligible mitochondria to the zygote.

A mixture of normal and mutant mtDNA within a cell or individual. Heteroplasmy arises from random segregation of mutant and wild-type mtDNA during cell division, affecting disease manifestation.

Typically asymptomatic (one functional allele is usually sufficient). In autosomal recessive IEMs, heterozygotes usually have sufficient enzyme activity from one allele to remain unaffected.

Nonsense. Nonsense mutations directly change a sense codon to a stop codon, unlike missense which alters amino acids without stopping translation.

Frameshift mutation. Loss of 2 nucleotides shifts the reading frame, as it is not a multiple of 3, altering all subsequent codons.

$ $ $\frac{1}{4}$. For autosomal recessive disorders, each child has a 25% chance of inheriting two mutant alleles from carrier parents.

$\frac{1}{2}$. With both parents as carriers, children have a 50% chance of being heterozygous carriers per Mendelian inheritance.