How would you find out that a particular disease/disorder is inherited and, if so, in which manner? Elaborate with suitable examples. (Answer in 350 words)

- How would you find out that a particular disease/disorder is inherited and, if so, in which manner? Elaborate with suitable examples. (Answer in 350 words)
Introduction
Establishing that a condition is inherited and determining how it is transmitted are two separate investigations, taken in that order. The first uses population and family comparison, the second the pedigree, and both are now confirmed at the molecular level.
Body
1. Establishing that it is inherited: compare the recurrence risk among relatives with the population prevalence, and compute the sibling relative risk. Twin studies separate genes from shared environment, since a substantially higher monozygotic than dizygotic concordance implies genetic contribution, as in schizophrenia at roughly 48 against 17 per cent. Adoption and half-sibling designs remove shared household effects, raised parental consanguinity points to recessive causation, and clustering in endogamous groups indicates founder effects.
2. Constructing the pedigree: record at least three generations from the proband outward, using standard symbols, squares for males, circles for females, filled for affected, a diagonal for the deceased, a double line for consanguineous unions, an arrow for the proband, with generations in Roman and individuals in Arabic numerals. Age at onset, sex ratio of the affected and stillbirths must be entered, and ascertainment bias allowed for, since families are usually found through an affected child.
3. Assigning the mode: autosomal dominant pedigrees show vertical transmission, an affected parent for every affected child, male-to-male transmission and equal sex incidence, as in Huntington disease and achondroplasia. Autosomal recessive pedigrees skip generations, show a one in four sib recurrence and frequent consanguinity, as in sickle cell disease and thalassaemia. X-linked recessive conditions affect males through carrier mothers with no male-to-male transmission, as in haemophilia A and Duchenne dystrophy. Mitochondrial disorders pass only through mothers. Multifactorial conditions cluster without a clean pattern and show risk falling steeply with kinship distance.
4. Confirming the assignment: karyotype, FISH and chromosomal microarray for aberrations; linkage and segregation analysis; targeted sequencing or exome sequencing for the causal variant; HPLC for haemoglobinopathies. This is what converts a pedigree inference into a counselling-grade diagnosis.
Conclusion
Aggregation establishes heritability; the pedigree assigns the mechanism; molecular testing verifies it. Skipping the first step is how familial environmental exposures are mistaken for genes.