Inheritance, chromosome biology, mutation mechanisms, and pathogenesis.
Chapters
The major histocompatibility complex (MHC) is the most polymorphic locus in the human genome: a ~4 Mb stretch on chromosome 6p21.3 encoding cellsurfac
The cell cycle is the ordered sequence of events by which a cell duplicates its contents and divides into two daughter cells. It consists of interphas
Gametogenesis is the formation of haploid gametes (eggs and sperm) from diploid germ cells through meiosis. Oogenesis and spermatogenesis differ drama
Meiosis is the specialized cell division that produces haploid gametes from diploid precursor cells. It involves two successive divisions: meiosis I (
Human chromosomes are organized structures of DNA wound around histone proteins into chromatin. The 46 human chromosomes (22 pairs of autosomes plus X
Structural chromosome rearrangements (translocations, deletions, duplications, inversions) fall into two big mechanistic camps. Recurrent rearrangemen
Cilia are surface organelles built around a microtubule core (the axoneme) anchored to a basal body (modified centriole). Almost every vertebrate cell
The PI3KAKTmTOR pathway controls cellular growth, proliferation, autophagy, and metabolism. Germline or somatic activation produces a recognizable fam
The RASMAPK pathway anchors one of the most clinically central signaling families in genetics because germline activating mutations along its length p
Neural crest cells delaminate from the dorsal lips of the closing neural tube during week 4, undergo an epithelialtomesenchymal transition (EMT), and
Neurulation is the folding of a flat sheet of dorsal ectoderm into the closed neural tube, the precursor to the entire CNS. It happens in two phases o
The trunk is built segmentbysegment by somites: paired blocks of paraxial mesoderm that bud off the unsegmented presomitic mesoderm in a strict headto
Embryology answers a single question: which developmental event went wrong? Almost every congenital malformation can be reverseengineered to a specifi
The heart is the first organ to function. By day 22 the linear heart tube is beating; by day 28 it has looped to the right (dextral looping); by week
Limb buds appear at week 4 (the upper buds first, day ~26; the lower buds 1–2 days later) and complete their basic patterning by week 8. Each bud is a
The pharyngeal apparatus is the embryologic origin of the face, jaw, ears, throat, larynx, and the endocrine glands of the neck (parathyroids, thymus,
Xinactivation (lyonization) is the process by which one of the two X chromosomes in 46,XX individuals is transcriptionally silenced to achieve dosage
Epigenetics refers to heritable changes in gene expression that do not involve changes in the DNA sequence. The two dominant molecular mechanisms are
Genomic imprinting is an epigenetic phenomenon in which gene expression depends on the parent of origin. Imprinted genes are silenced on one parental
Uniparental disomy (UPD) occurs when both copies of a chromosome (or chromosomal region) are inherited from the same parent. It can cause disease thro
Autosomal dominant (AD) inheritance requires only one pathogenic allele on an autosome to cause disease. Affected individuals typically have one affec
Autosomal recessive (AR) inheritance requires two pathogenic alleles (one from each parent) for disease expression. Carriers (heterozygotes) are typic
Xlinked inheritance involves genes on the X chromosome. Because males are hemizygous (only one X), a single pathogenic variant causes full disease exp
Genetic heterogeneity describes the situation in which different genetic causes can produce the same (or very similar) phenotype. It is the conceptual
Autosomal dominant disease can be caused by several distinct molecular mechanisms. The two most clinically central are haploinsufficiency and dominant
Penetrance is the probability that an individual carrying a particular genotype will manifest the corresponding phenotype. It is a populationlevel sta
Pleiotropy is the phenomenon of a single gene producing multiple, often unrelated phenotypic effects. The classic teaching example is sickle cell dise
Variable expressivity is the range of phenotypic features and severity observed among individuals who all manifest a given condition (i.e., all are pe
Mitochondrial inheritance follows a strictly maternal pattern because mitochondria are transmitted through the oocyte cytoplasm. Pathogenic variants c
Mosaicism is the presence of two or more genetically distinct cell populations in an individual derived from a single fertilized egg. The timing of th
Multifactorial (complex) inheritance involves the combined effects of multiple genetic variants and environmental factors. These conditions do not fol
Trinucleotide repeat disorders are caused by expansion of short tandem DNA repeats (most commonly 3nucleotide units) beyond a pathogenic threshold. A
DNA replication is a semiconservative process that duplicates the genome before cell division, with an intrinsic error rate reduced to approximately 1
Transcription is the synthesis of RNA from a DNA template by RNA polymerase. In eukaryotes, transcription occurs in the nucleus and is tightly regulat
Translation is the synthesis of protein from an mRNA template, performed by ribosomes in the cytoplasm (or at the rough endoplasmic reticulum for secr
DNA is a polymer of deoxyribonucleotides organized into an antiparallel double helix and packaged into chromatin. Its structural features (base compos
A eukaryotic gene is more than its coding sequence: it is a transcription unit (promoter, exons, introns, UTRs, polyadenylation signal) embedded in a
The mitochondrial genome (mtDNA) is a 16.5 kb circular, doublestranded DNA molecule present in hundreds to thousands of copies per cell. It encodes 37
Most of the transcribed human genome does not encode protein. Noncoding RNAs (ncRNAs) regulate gene expression, chromatin structure, and translation.
Gene expression is the process by which information encoded in DNA is converted into functional products (primarily proteins). It involves transcripti
Fetal alcohol spectrum disorder is the umbrella term for the range of neurodevelopmental and structural abnormalities caused by prenatal alcohol expos
Infectious teratogens cause structural and neurodevelopmental anomalies through several mechanisms: direct cytopathic effect on developing tissues, in
Maternal metabolic conditions (diabetes, phenylketonuria, hyperthermia) and environmental physical exposures (radiation, recreational substances) disr
Medication teratogens are the most clinically prominent teratology category because the embryopathies are wellcharacterized and many drugs have safer
A teratogen is any agent (drug, infection, maternal metabolic disturbance, or physical exposure) that disrupts normal embryologic or fetal development
