Gene mutations. Chromosomal syndromes and diseases. Blastopathies - double malformations.
A gene mutation is the permanent alteration in DNA sequence that makes up a gene. There are two main classifications:
- Hereditary (inherited from a parent, affecting every cell, also known as germline mutations)
- Acquired (or Somatic) that occur at some point in the person's life, can be an error in DNA replication or repair
Mutations can affect single genes, or the chromosomes themselves, types of genetic mutation are:
- Missense - wrong protein coded for
- Nonsense - stop codon coded for
- Insertion/micro deletion- frameshift mutations
- Micro Duplication
- Repeat expansion
Alternatively, we can have structural chromosomal mutations, also known as structural mutations, these are errors on a chromosomal level rather than a simple base pair level:
- Deletion
- Duplication
- Inversion
- Translocation
Structural chromosome mutations: deletion, duplication and inversion within one chromosome; insertion and reciprocal translocation between two.
Image: “Chromosomes mutations-en” by G YassineMrabet Talk ✉ This W3C-unspecified vector image was created with Inkscape ., Public domain, via Wikimedia Commons.
Humans are also susceptible to chromosomal aneuploidy, this is where the total number of chromosomes is not the normal 46. Where we see Trisomy (e.g. Trisomy 8, 9, 13, 18 or 21) we get 47 chromosomes, and where we have Monosomy (e.g. Monosomy X - Turner syndrome) we have 45 chromosomes. These result in structural and functional errors in fetal development.
Memory aid: the three autosomal trisomies seen in live births: Patau 13, Edwards 18, Down 21 ("Puberty at 13, Elections at 18, Drinking at 21"). Down syndrome is the most common; Patau and Edwards are usually fatal in infancy. Sex chromosome examples: Turner 45,X and Klinefelter 47,XXY.
Blastopathy
Blastopathies occur during the first 15 days following fertilisation. The most frequent cause is a chromosomal aberration in combination with environmental factors. The effects can be varied:
- Superficial or deep implantation of blastocyst in uterine wall
- Disturbance of embryo orientation
- Empty embryo sacs
- Double malformations (conjoined twins)
Remember: double malformations are conjoined twins, from incomplete splitting of one embryo (monozygotic twins dividing late, after about day 13). They are named by the joined region plus -pagus: thoracopagus (chest, most common), omphalopagus (abdomen), craniopagus (head), pygopagus (sacrum), ischiopagus (pelvis). In asymmetric forms an incomplete parasitic twin hangs on a normal one.