Autosomal aneuploidy refers to a genetic condition where a person has an abnormal number of non-sex chromosomes. Human cells normally contain a specific count of chromosomes, which carry our genetic information. When this count deviates from the typical number, it can lead to variations in development and function.
Understanding Autosomal Aneuploidy
Chromosomes are thread-like structures found inside the nucleus of animal and plant cells, composed of DNA and proteins. They carry genes, which contain instructions for building and maintaining an organism. Humans typically have 46 chromosomes arranged in 23 pairs within most body cells. One set of 23 chromosomes comes from the mother and the other from the father.
These 23 pairs are divided into two categories: sex chromosomes and autosomes. Sex chromosomes, typically X and Y, determine an individual’s biological sex. The remaining 22 pairs are autosomes, numbered 1 through 22, generally from largest to smallest. Autosomes contain genes that govern most general characteristics, distinct from those related to sex determination.
Aneuploidy describes a condition with an abnormal number of chromosomes in a cell. For example, a human cell might have 45 or 47 chromosomes instead of 46. When a chromosome is missing from a pair, the condition is called monosomy. If there is an extra copy of a chromosome, resulting in three copies instead of two, it is termed trisomy.
How Autosomal Aneuploidy Occurs
Autosomal aneuploidy primarily arises from errors during cell division, a process known as nondisjunction. Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly. This can occur during meiosis, which creates egg and sperm cells, or during mitosis, the division of somatic (body) cells.
During meiosis, if nondisjunction occurs, a gamete (sperm or egg cell) may end up with an abnormal number of chromosomes. For instance, an egg or sperm might have 22 or 24 chromosomes instead of the normal 23. If such an abnormal gamete combines with a normal one during fertilization, the resulting embryo will have an abnormal chromosome count. Nondisjunction in meiosis I, where homologous chromosomes fail to separate, can result in two gametes with an extra chromosome and two gametes missing a chromosome. In meiosis II, if sister chromatids fail to separate, it can lead to two normal gametes, one with an extra copy, and one with a missing copy.
Nondisjunction can also happen during mitosis, affecting body cells after fertilization. When this occurs, not all cells in the body will have the abnormal chromosome number. Instead, an individual will have a mixture of cells with different genetic compositions, a condition called mosaicism. The effects of mosaicism can vary widely depending on the proportion and distribution of affected cells throughout the body.
Common Autosomal Aneuploidy Syndromes
Autosomal aneuploidies often lead to developmental and health challenges, with many forms resulting in miscarriage. However, some specific autosomal trisomies are observed in live births. The most common involve chromosomes 13, 18, and 21.
Trisomy 21 (Down Syndrome)
Trisomy 21, known as Down syndrome, is the most frequent chromosomal anomaly in humans, affecting approximately 1 in 700 live births globally. Individuals with Down syndrome have an extra full or partial copy of chromosome 21. This extra genetic material impacts physical and intellectual development, leading to characteristic facial features, mild to moderate intellectual disabilities, and an increased risk for certain health issues like congenital heart defects, gastrointestinal abnormalities, and vision or hearing problems.
Trisomy 18 (Edwards Syndrome)
Trisomy 18, known as Edwards syndrome, is a severe genetic condition caused by an extra copy of chromosome 18. This syndrome is rarer than Down syndrome, occurring in about 1 in 5,000 to 6,000 live births. Babies with Edwards syndrome often present with low birth weight, a small head, low-set ears, overlapping fingers, and heart and kidney problems. Most infants with full Trisomy 18 do not survive past their first year, with many dying before or shortly after birth.
Trisomy 13 (Patau Syndrome)
Trisomy 13, known as Patau syndrome, is the most severe and least common of the viable autosomal trisomies, affecting approximately 1 in 4,000 to 1 in 16,000 live births. This condition is caused by an extra copy of chromosome 13. Infants with Patau syndrome typically have severe intellectual and physical problems, including craniofacial defects like cleft lip and palate, brain and spinal cord abnormalities, small eyes, extra fingers or toes, and severe heart defects. The median survival for infants with Patau syndrome is often less than a few days, with a very small percentage surviving beyond the first year.
Health Impacts and Detection
Autosomal aneuploidy significantly impacts health, often leading to developmental disorders and medical problems. These can include growth failure, intellectual disabilities, and issues affecting multiple organ systems, such as congenital heart defects, kidney abnormalities, and skeletal differences. The specific health implications vary depending on which chromosome is affected and the extent of the chromosomal imbalance.
Identifying autosomal aneuploidy involves several diagnostic methods. Karyotyping is a traditional technique where a picture of a person’s chromosomes is created to check their number and structure. This test can reveal extra or missing whole chromosomes. Prenatal screening tests, such as Non-Invasive Prenatal Testing (NIPT), analyze cell-free DNA from the mother’s blood to assess the risk of certain trisomies like Trisomy 21, 18, and 13. NIPT is a screening tool, and positive results usually require confirmation through more definitive diagnostic tests.
Diagnostic tests like chorionic villus sampling (CVS) and amniocentesis provide a definitive diagnosis by obtaining fetal cells for chromosomal analysis. CVS, performed between 11 and 14 weeks of gestation, involves taking a small sample of placental tissue. Amniocentesis, done after 15 weeks, involves collecting a sample of amniotic fluid. Both procedures carry a small risk of miscarriage, generally less than 0.5%. These invasive tests allow for a detailed examination of fetal chromosomes, confirming the presence and type of aneuploidy.