6.5 Meiosis, Variation and Non-disjunction

Meiosis produces haploid nuclei from a diploid parent so fertilization can restore rather than double chromosome number. DNA replicates once before meiosis, followed by two nuclear divisions. In prophase I homologous chromosomes pair as bivalents. Each bivalent contains two homologues and four chromatids; one homologue was inherited from each parent and may carry different alleles at corresponding loci.

Non-sister chromatids can break and rejoin at corresponding positions, producing crossing over. Visible attachment regions are chiasmata. Reciprocal exchange creates recombinant chromatids with new linked allele combinations; it does not exchange genes between arbitrary non-homologous locations. Homologue pairing also helps ensure the correct partners attach to opposite spindle poles.

At metaphase I each bivalent orients independently of the others. At anaphase I homologous chromosomes separate while sister centromeres remain joined, halving chromosome number. Telophase I and cytokinesis may follow. Each resulting nucleus is haploid even though every chromosome still has two chromatids.

No second S phase occurs. Chromosomes align individually at metaphase II, centromeres divide at anaphase II and sister chromatids separate. Telophase II and cytokinesis yield four haploid nuclei. Crossing over means former sisters may no longer be genetically identical, so calling meiosis II simply 'mitosis' can hide an important difference in starting material.

Independent orientation produces 2ⁿ possible maternal/paternal chromosome combinations for n homologous pairs, before crossing over is counted. Humans therefore have 2²³ combinations from orientation alone. Crossing over generates far more within-chromosome combinations, and random fertilization combines any one genetically varied gamete from each parent.

Mendel's law of segregation reflects separation of the two alleles carried on homologous chromosomes into different gametes. Independent assortment applies most directly to genes on different chromosomes, because bivalents orient independently. Genes close together on one chromosome are linked and do not assort independently unless recombination separates their alleles.

Non-disjunction occurs when homologues fail to separate in anaphase I or sister chromatids fail in anaphase II. The resulting gametes can be n+1 or n−1. Fertilization with a normal gamete produces aneuploid zygotes such as a trisomy or monosomy. Trisomy 21 causes Down syndrome; risk and phenotype cannot be inferred merely from the physical size of the extra chromosome.

The product pattern identifies the stage of error. Failure in meiosis I makes all four gametes abnormal: two n+1 and two n−1. Failure in one meiosis-II cell gives two normal gametes, one n+1 and one n−1. Karyotyping can reveal chromosome-number changes, using fetal cells obtained through procedures such as chorionic villus sampling or amniocentesis when clinically indicated.