Genetics and Chromosomal Inheritance: Pedigree, Linkage, and Bacterial Genetics

Pedigree

a diagram showing the occurrence of phenotypes (and sometimes genotypes) in several generations of a family.

Proband

the individual from whom a pedigree is initiated (often the first affected family member coming to medical attention).

Autosomal dominant / autosomal recessive

patterns of inheritance for traits located on autosomes (non-sex chromosomes).

X-linked dominant / X-linked recessive

inheritance patterns for traits on the X chromosome.

Carrier

a heterozygous individual who carries a recessive allele but does not express the phenotype.

Consanguinity

mating between individuals who are closely related, often increasing chance of recessive traits appearing.

Penetrance

the proportion of individuals with a particular genotype who actually express the expected phenotype.

Expressivity

the degree to which a genotype is phenotypically expressed (variation in severity).

Lethal allele

an allele that causes death (usually embryonic or early) when present in certain genotype(s).

Genetic testing / diagnostic testing / predictive testing / carrier testing

different types of tests to identify genotypes, risk, or carriers.

Prenatal diagnosis

testing of a fetus to detect genetic defects before birth.

Noninvasive prenatal testing (NIPT)

testing fetal DNA in maternal blood to screen for chromosomal abnormalities.

Genetic linkage

when two genes are close together on the same chromosome and tend to be inherited together.

Linkage group

the set of genes on a single chromosome that tend to be inherited together.

Recombination (crossover)

the exchange of genetic material between homologous chromosomes during meiosis.

Recombinant (nonparental) gamete / individual

offspring whose combination of alleles differs from the parents because of recombination.

Parental (nonrecombinant) gamete / individual

offspring showing the original (parental) allele combinations.

Recombination frequency

the proportion of recombinant offspring among total offspring; used to estimate genetic distance.

Map unit (centimorgan, cM)

a unit of genetic distance; 1 cM ≈ 1% recombination frequency.

Interference

when one crossover event in a region reduces the probability of another crossover nearby.

Coefficient of coincidence

observed double crossovers divided by expected double crossovers; interference = 1 − coefficient.

Three-point test cross

test cross involving three genes to determine gene order and recombination frequencies.

Double crossover

an event in which two crossovers occur between genes, which can obscure mapping if not accounted.

Aneuploidy

gain or loss of one or more individual chromosomes (not whole sets).

Euploidy

the complete set of chromosomes (correct number).

Polyploidy

having more than two complete sets of chromosomes (e.g. triploid, tetraploid).

Monosomy

loss of a single chromosome (2n − 1).

Trisomy

gain of a single chromosome (2n + 1).

Nullisomy

loss of both homologs of a chromosome pair (2n − 2).

Structural chromosome rearrangements

changes in chromosome structure (deletions, duplications, inversions, translocations).

Deletion

loss of a chromosome segment.

Duplication

doubling of a chromosome segment.

Inversion

a segment that is reversed in orientation.

Translocation

movement of a chromosome segment to a nonhomologous chromosome (reciprocal, Robertsonian).

Robertsonian translocation

fusion of long arms of acrocentric chromosomes, often losing the short arms.

Genomic imprinting

expression of a gene depending on whether it's inherited from the mother or father.

Mosaicism

presence of two or more different cell lines (with different karyotypes) within one individual.

Prokaryote / Bacteria

organisms without a membrane-bound nucleus, with generally circular chromosomes.

Plasmid

small, usually circular, extra-chromosomal DNA molecule that replicates independently in bacteria.

Conjugation

direct transfer of DNA (often plasmids) between bacteria via physical contact (e.g. sex pilus).

Transformation

uptake of free DNA from the environment by bacteria.

Transduction

transfer of bacterial DNA via bacteriophages (viruses).

Hfr (High frequency recombination) strain

bacterial strain in which the F plasmid is integrated into the chromosome, enabling chromosomal gene transfer during conjugation.

F (fertility) factor / F plasmid

plasmid that confers ability to form a pilus and donate DNA in conjugation.

F′ (F prime) plasmid

a plasmid that carries some chromosomal genes (when F integrates and excises imprecisely).

Generalized transduction

phage packages random bacterial DNA by mistake and transfers it.

Specialized transduction

phage transfers only specific bacterial genes adjacent to its integration site.

Lytic cycle

viral replication cycle leading to destruction (lysis) of the host cell.

Lysogenic cycle (lysogeny)

viral DNA integrates into host genome and is replicated passively; may later enter lytic cycle.

Temperate phage

phage that can undergo lysogeny.

Competence (bacterial)

the ability of a bacterial cell to take up extracellular DNA.

Transposable element / transposon

DNA sequences that can move (transpose) within the genome.

Why can recombination frequencies never exceed 50%?

Independent assortment produces 50% recombinant gametes. Beyond this, linked genes appear unlinked because crossing over randomizes combinations.

How do you use a three-point cross to determine gene order and distance?

Identify the parental and double crossover classes. The gene that differs in double crossovers is in the middle. Then calculate recombination frequencies for adjacent genes.

Explain interference and how the coefficient of coincidence is used.

Coefficient of coincidence = observed double crossovers ÷ expected. Interference = 1 − COC. Positive interference means fewer double crossovers than expected.

How does linkage distort expected Mendelian ratios?

Linked genes don't assort independently; parental combinations occur more frequently than predicted by 9:3:3:1 or 1:1:1:1 ratios.

What are the limitations or sources of error in genetic mapping?

Multiple crossovers can go undetected, recombination frequencies underestimate large distances, and small sample sizes cause error.

What are the effects of monosomy and trisomy on viability in humans?

Most are lethal. Common survivable trisomies include Down syndrome (trisomy 21), Edwards (18), and Patau (13). Monosomy of autosomes is usually lethal; Turner syndrome (XO) is survivable.

How does nondisjunction lead to aneuploidy, and during which meiotic division can it occur?

Homologs (in meiosis I) or sister chromatids (in meiosis II) fail to separate, resulting in gametes with extra or missing chromosomes.

Explain how duplications and deletions can lead to gene dosage effects.

Extra copies (duplication) can overexpress genes, while deletions can reduce expression or unmask recessive alleles.

How would you use cytogenetic techniques (karyotyping, FISH) to detect structural rearrangements?

Karyotyping identifies large deletions/duplications. FISH uses fluorescent probes to detect specific sequences or translocations.

Paracentric inversion

Excludes the centromere.

Pericentric inversion

Includes the centromere.

Position effects

Moving genes to a new environment may alter expression (e.g., placing a gene near heterochromatin or breaking a coding sequence).

Mosaicism

Some cells carry the abnormality while others don't, leading to milder or variable phenotypes.

Conjugation

Direct plasmid transfer by contact.

Transformation

Uptake of free DNA from the environment.

Transduction

DNA transfer via bacteriophages.

Hfr strain

Hfr cells transfer chromosomal DNA in order; interrupted mating experiments reveal gene order and map distances.

Interrupted mating experiments

Conjugation is stopped at timed intervals to allow relative order mapping of genes.

Specialized transduction

Only transfers bacterial genes adjacent to the prophage integration site.

Generalized transduction

Can move any gene.

Lysogeny

Viral DNA integrates into the host genome (prophage), replicating along with host DNA until triggered into the lytic cycle.

Plasmids

Often carry resistance genes, virulence factors, or metabolic traits, spreading them rapidly by conjugation.

Autosomal recessive traits

Usually skip generations, appear in both sexes equally, and are more common with consanguinity.

Autosomal dominant traits

Appear in every generation, affect both sexes equally, and an affected person typically has at least one affected parent.

X-linked recessive pedigree

Males are more often affected because they have only one X chromosome.

Incomplete penetrance

Not everyone with the genotype shows the phenotype; other genetic or environmental factors affect expression.

Variable expressivity

Neurofibromatosis may cause mild skin spots in one person but severe tumors in another, complicating pedigree interpretation.

Consanguinity

Relatives are more likely to share the same recessive alleles, increasing the chance of homozygous recessive offspring.

Ethical considerations in genetic testing

Issues include privacy, discrimination, informed consent, potential psychological impact, and decisions about pregnancy continuation.