Biomedical Genomics Quiz 1

Pedigree Symbol

Unaffected male

Pedigree Symbol

Unaffected Female

Pedigree Symbol

Affected Male

Pedigree Symbol

Affected Female

Pedigree Symbol

Sibship

Pedigree Symbol

Consanguineous Mating

Pedigree Symbol

Proband

Pedigree Symbol

Autosomal Dominant

Pedigree Symbol

Autosomal Recessive

Consanguinity

A reproductive union between two individuals who are biological blood relatives.

Proband

Individual in a family who is first identified for having a genetic condition.

Modes of Inheritance

Autosomal Dominant, Autosomal Recessive, X-Linked Dominant, X-Linked Recessive, Mitochondrial

Autosomal Dominant Inheritance

• Only one copy of the mutated gene from a single parent causes the condition

• Vertical pattern

• Appears in every generation

Autosomal Recessive Inheritance

• Two copies of the mutated gene (one from each parent) are required for the condition to appear

• Horizontal pattern

• Often skip generations

X-Linked Inheritance

A genetic trait or inherited gene located on and passed down the X chromosome. Affects males more than females.

Mitochondrial Inheritance

Transmission of mitochondrial DNA (mtDNA) from mother to her offspring.

De Novo Inheritance

Genetic mutation occurs for the first time in an individual, not inherited from parents.

Common Variant types

SNPs, Indels, CNVs

SNPs

Single Nucleotide Polymorphisms, variations at a single nucleotide position in a DNA sequence

INDELs

Insertion or deletion of one or more nucleotides or base pairs

CNVs

Copy Number Variants, the number of copies of a segment of DNA differs between individuals. There are two copies (one inherited from each parent), a person may have one, three, or more copies of that same DNA segment.

Structural Variants

Large-scale genomic alterations: insertions, deletions, duplications, inversions

Somatic Mutations

Mutations occurring in somatic cells, not inherited, and can lead to cancer and other diseases.

Germline Mutations

Mutations occurring in germ cells, which are inherited and can be passed on to offspring.

Point Mutation

Affects only one nucleotide in a DNA sequence, classified as Transitions and Transversions

Transitions

A purine is replaced by a purine base, or a pyrimidine is replaced by a pyrimidine base

Transversions

A purine base is replaced by a pyrimidine base (or vice versa) in a DNA sequence

Purine Bases

Adenine (A) and Guanine (G)

Pyrimidine Bases

Cytosine (C), Thymine (T), and Uracil (U)

Inversions

A DNA segment is reversed in its orientation within a chromosome

Consequences of Point Mutations

Silent Mutations, Missense Mutations, Nonsense Mutations

Silent Mutations

Produce no change in amino acid sequence, does not affect protein function

Missense Mutations

• Result in a different amino acid, affects protein function

• Conserved = similar amino acid properties

• Non-Conserved = dissimilar amino acid properties

Nonsense Mutations

Generates a stop codon, premature termination of translation.

Consequences of INDELs

Frameshift Mutations

Frameshift Mutations

Shifts reading frame of protein coding region, causes changes in amino acid sequence, may produce nonfunctional protein

Frameshift Mutation effect on Phenotype

Null Allele, Hypomorph, Hypermorph

Null Allele

No protein is made, or protein is non-functional, Loss of Function

Hypomorph

Protein has reduced function, Loss of Function

Hypermorph

Protein has increase function, or different function, Gain of Function

Polgenic Models

Models involving multiple genes that contribute to a specific trait or phenotype

Monogenic Models

Models involving a single gene that contributes to a specific trait or phenotype.

FASTQ

Raw, unaligned reads and quality scores

CIGAR Strings

(in BAM/SAM) shows how sequences align to a reference sequence, indicating matches, mismatches, insertions, and deletions.

BAM

Compressed, aligned sequencing reads

VCF

Table of called variants (chromosome, position, ref/alt allele, annotations)

Modes of Inheritance

Classic Mendelian, Incomplete Dominance, Codominance, Polygenic / Multifactorial

Classic Mendilian Inheritance

Follows Mendel’s laws, single-gene traits passed from parents to offspring

Incomplete Dominance

Heterozygous genotype results in phenotype that shows intermediate between dominant and recessive traits.

Codominance

Both alleles in heterozygous genotype express themselves equally in the phenotype.

Polygenic / Multifactorial Inheritance

Multiple genes influence a trait, resulting in a range of phenotypes, bell-shaped trait distributions (skin or height color)

Reference Genome

Used to align sequencing reads, not identical to any one individual, updated periodically to improve representation of diverse populations,