In this article we will discuss about the inversions in humans which occurs when the genes in a section of a chromosome is reversed.
Pericentric Inversion:
There are a number of reports of pericentric inversions in human. Breaks occur in both, short (p) and long (q) arms of the chromosomes. The length of inverted segment can be precisely identified by the study of banding patterns of the normal and the inverted chromosomes and their recombinants.
If the inverted segment is very small, it remains unpaired (asynapsis) and crossing over does not occur within this segment. Such inversions are quickly propagated and may remain undetected. On the other hand, if the inverted segment is large enough to permit pairing of inverted regions by loop formation, crossing over can occur within the loop leading to the production of deficiency-duplication chromatids.
Smaller deficiencies can be tolerated be the progeny carrying them. Such individuals show partial monosomy for the deficient region and partial trisomy for the duplicated region of the chromosome. A case of pericentric inversion was reported by Vianna-Morgante and associates in 1976.
A female was the carrier of a pericentric inversion for chromosome 18, the break points were located in the band 1 of region 1 of the short arm (p11) and in the band 1 of region 2 of the long arm (q21) (Fig. 15.13).
The inverted segment consisted of about 60% of the total length of chromosome 18. Thus her chromosome constitution can be written as 46, XX, inv (18) (pi 1 q21) or 46, XX, inv (18) (pterp11 :: q21 p11 :: q21qter). The centromere position in normal chromosome is sub-median but it became median in the inverted chromosome.
Chromosome pairing occurred through loop formation. Crossing over in the inversion loop produced recombinant chromatids having deficiency-duplication.
One of her offspring’s carried the recombinant chromosome with duplication of the terminal segment of the short arm and deletion for the distal 1/3 of the long arm (Fig. 15.13 D). The chromosome constitution can be written as: 46, XY, -18, +rec (18), (pterq12 :: p 11 —>pter), inv (18) (p11 q 12) mat. This male child showed the characteristics of partial monosomy and partial trisomy for chromosome 18.
The child was hypotonic with severe developmental retardation and multiple congenital anomalies. He had brachycephaly; sparse, thin, short hair; flat nasal bridge; prominent forehead; carp-shaped mouth; ears with small tragus, and hypoplastic appearance of genitalia etc. There was a high frequency of whorls (7/10) on digital areas.
The second child of this woman was a girl who carried a recombinant chromosome; she was trisomic for the distal 1/3 of long arm and monosomic for the terminal region of short arm of chromosome 18 (Fig. 15.13 E). Her chromosome constitution can be written as : 46, XX, -18 + rec (18), (qter q21 :: p11 q12 :: q21 àqter) inv (18) (pll q21) mat.
She was examined at the age of 3½ years and showed mental retardation with multiple abnormalities. She had multiple haemangiomata, flat supraorbital ridges, asymmetrical face, cornpactodactyly of the 5th digit on both hands, flat feet, syndactyly between 3rd and 4th toes of cleft foot, hypo plastic labia majora etc. Simple arches were present in all the digits. Thus the carriers of inversion have high risk for the production of unbalanced progeny.
Paracentric Inversion in Human:
In human, paracentric inversions are estimated to occur with a frequency of 1 in 2000 to 1 in 3500 persons. They have been reported for several chromosomes, such as, chromosomes 3, 5, 7, 8, 9, 13 and 14. Progeny of paracentric inversion heterozygotes may contain dicentric or mono-centric recombinants with duplications and deficiency.
Worsham et al. in 1989 reported a dicentric recombinant chromosome 9 in a female child; this chromosome was derived from a paracentric inversion. The mother, maternal grandmother and 3 maternal aunts were carriers for this inversion. This paracentric inversion was in the long arm (q) of chromosome 9 where the bands 22.1 34.3 were inverted.
The mothers karyotype was 46, XX, inv (9) (q22.1 q34.3). Karyotype of the affected child (pro-band) was 46, XX, rec (9) dup p, inv (9) (q22.1 q34.3). The dicentric chromosome 9 had deficiency and duplication. It was formed due to a crossing over in the inversion loop along with crossing over in the interstitial region. The dicentric recombinant was included in the ovum.
Paracentric inversions have no remarkable phenotypic effects on the individual carrying them but abortions may occur. The progeny often show remarkable phenotypic effects because they may contain a recombinant dicentric or mono-centric chromosome carrying duplication and deficiency.
In the above case, the progeny showed multiple malformations, e.g., lowest posteriorly rotated ears, left pupil larger than the right, thin lower lips, high arched palate, hypo plastic finger nails, significant myopia, micrognathia and umbilical hernia.