Human Chromosome Number
Normal human cells contain 46 chromosomes, consisting of 23 pairs: 22 pairs of autosomes and 1 pair of sex chromosomes (XX in females or XY in males). 1, 2
Standard Chromosomal Complement
The diploid human chromosome number of 46 was definitively established in 1956, ending three decades of incorrect belief that humans had 48 chromosomes 1, 2. This fundamental discovery forms the foundation of modern human cytogenetics and our understanding of chromosomal disorders 1.
- Each human cell nucleus contains 46 chromosomes organized as 23 pairs 3
- 22 pairs are autosomes (numbered 1-22 by size) 4
- 1 pair consists of sex chromosomes: XX in females, XY in males 5, 4
Chromosomal Sex Determination
Biological sex is primarily determined by sex chromosome complement, with females typically having two X chromosomes (XX) and males having one X and one Y chromosome (XY). 5
- Sex chromosome variations occur in approximately 1 in 400 to 1 in 1,000 individuals 5
- Males are hemizygous for the X chromosome, making them more susceptible to X-linked recessive conditions 6
- In females, one X chromosome undergoes random inactivation (lyonization) in each cell, though approximately 23% of X chromosome genes escape this inactivation 6
Chromosomal Abnormalities in Disease
Deviations from the normal 46-chromosome complement are major causes of developmental disorders, pregnancy loss, and certain malignancies. 6
Common Numerical Abnormalities:
- Hyper-diploid conditions: 47-75 chromosomes, often involving multiple trisomies 6
- Non-hyper-diploid conditions: fewer than 46 chromosomes or specific translocations 6
- Chromosome abnormalities are detected in approximately 3-5% of individuals with developmental delay or mental retardation 6
Clinical Testing Considerations:
Karyotype analysis at 400-550 band resolution remains the standard initial cytogenetic test, capable of identifying all 46 chromosomes and detecting structural abnormalities. 6
- Higher resolution analysis (850-band) may be needed for subtle abnormalities 6
- 24-color karyotyping techniques allow unique color labeling of each chromosome pair for enhanced detection of structural rearrangements 6
- Subtelomeric FISH analysis using 41 unique probes can detect cryptic rearrangements near chromosome ends 6
Important caveat: Parents of individuals with structural chromosomal abnormalities should undergo chromosome analysis to determine if they carry balanced rearrangements, which has implications for recurrence risk 6.