In the human XX-XY sex determination system, the father determines offspring sex because he contributes either an X chromosome (producing a daughter) or a Y chromosome (producing a son). Birds and butterflies use the ZW-ZZ system, the reverse of humans, where the female (ZW) is heterogametic and determines offspring sex. Grasshoppers use the XX-XO system, where males (XO) have one fewer chromosome than females (XX) due to the absence of any Y chromosome. Males are hemizygous for X-linked genes, meaning any recessive allele on their single X chromosome is expressed with no masking allele, making X-linked recessive disorders such as haemophilia A and colour blindness more common in males. A carrier female ($X^A$ $X^a$) passes the recessive allele to half her sons (who become affected) and half her daughters (who become carriers), while an affected father passes his X chromosome to all daughters (making them carriers) and his Y to all sons (who are unaffected). Sickle cell anaemia results from a point mutation in the HBB gene on chromosome 11 that changes mRNA codon 6 from GAG (glutamic acid) to GUG (valine), causing HbS to polymerize under low oxygen and distort red blood cells into a rigid sickle shape. Down syndrome (karyotype 47, +21) is caused by trisomy of chromosome 21, an autosome, resulting from non-disjunction during meiosis, and presents with intellectual disability and characteristic facial features in both sexes. Turner syndrome (45, XO) is monosomy of the X chromosome, always producing a female phenotype (no Y chromosome, no SRY gene) with short stature, webbed neck, and infertility. Klinefelter syndrome (47, XXY) is always male because the Y chromosome carries the SRY gene that determines maleness, despite the presence of two X chromosomes, and presents with gynaecomastia and reduced fertility. The distinction between Mendelian disorders (single-gene mutations following Mendelian ratios) and chromosomal disorders (aneuploidy detectable by karyotyping) is fundamental to understanding the inheritance and diagnosis of all genetic diseases tested in NEET.