Lec 7 structural abnormalities.pptx (4).pdf

MGD MODULE CHROMOSOMAL ABNORMALITIES STRUCTURAL ABNORMALITIES DR.DHAMYA K. KADHIM  Republic of Iraq Ministry of Higher Education Stage:S2 and Scientific Research Module: MGD Wasit Universty College of medicine...

MGD MODULE CHROMOSOMAL ABNORMALITIES STRUCTURAL ABNORMALITIES DR.DHAMYA K. KADHIM  Republic of Iraq Ministry of Higher Education Stage:S2 and Scientific Research Module: MGD Wasit Universty College of medicine :Lecture Title Chromosomal abnormalities Structural abnormalities Lecturer Name: Dr –Dhamyaa K. Kadhim Structural abnormalities Structural chromosomal abnormalities result from breakage and incorrect rejoining of chromosomal segments. A range of structural chromosomal abnormalities result in disease. The environmental factors responsible for structural abnormalities are mainly: Ionizing radiation ultraviolet light Chemical agents Viral infections  Patient Ascertainment i.e. Main Indications for routine chromosome investigation Constitutional (congenital) abnormalities 1)Prenatal screening – Down’s syndrome, especially raised maternal age (>35 years) – family history of chromosome abnormality – abnormal ultrasound scan of foetus 2)Birth defects – malformations – mental retardation 3)Abnormal sexual development e.g. Klinefelter’s syndrome 4)Infertility 5)Recurrent fetal loss Acquired abnormalities 6)Leukaemia and related disorders Structural abnormalities-cont’d Structural Abnormalities involved two main types: Balanced rearrangement : the exchange or rearrangement of genetic material does not cause any missing or extra genetic material: ✔ Balanced rearrangement are generally harmless with the exception of some cases in which one of the breakpoints damages an important functional genes. ✔ Balanced rearrangement carriers are often at risk of producing children with an unbalanced chromosomal complement. Structural abnormalities-cont’d Unbalanced rearrangement : In which the chromosomal complement contains an incorrect amount of chromosomal material and usually associated with very severe clinical effects. Types of structural abnormalities 1) Deletion-loss of genetic material results in monosomy for this segment of chromosome and usually large deletion will be incompatible with survive to term. ✔ Terminal deletion: involves a single break of the terminal part of chromosome and broken part is subsequently lost ✔ Interstitial deletion: involves two breaks and the intervening portion of the chromosome is lost. Terminal deletion Interstitial deletion  Types of structural abnormalities Terminal Deletion: Cri-du Chat syndrome (46,XX,5p- or 46,XY,5p-) ✔ It results from deletion of a short arm of chromosome number 5 ✔ The incidence 1per 20, 000 birth to 1per 50 000 birth. ✔ Underdevelopment of larynx hence affected new born make characteristic cat like cry (Mewing cry) ✔ Mental retardation ✔ Microcephaly and facial anomalies Types of structural abnormalities Terminal Deletion: Cri-du Chat syndrome (46,XX,5p- or 46,XY,5p-) G-banding karyotype of 46,XX,5p-  Types of structural abnormalities ✔ Interstitial deletion Some of deletion occur as micr-deletion which can not be detected by Karyotype. It is needed FISH technique for detection. e.g. Prader-Willi: interstitial deletion of paternal chromosome 15 (15q11–q13) & Angelman syndromes: interstitial deletion of maternal chromosome 15 (15q11–q13)  Structural abnormalities-cont’d 2) Duplication: extra copies of a chromosome part 3) Inversion: It involves two breaks along the chromosome in which a given segment is reversed in duplication position ✔ Pericentric inversion: inverted segment involved both p & q arms with centromere. ✔ Paracentric inversion: inverted segment involved only one arm. Pericentric inversion Paracentric inversion  Types of structural abnormalities 4) Ring chromosome: loss of telomeres or ends of both arms of chromosome and formation of a ring structure 5) Isochromosome: creation of two non- identical chromosomes, one is a combination of the two short arms, the other a combination of the two long arms. New chromosome in which the two arms genetically similar.  Types of structural abnormalities 5) Isochromosome: G-banding karyotype of 46, X, i (Xq) Turner syndrome  Types of structural abnormalities 6) Insertion -no loss of genetic material, but a rearrangement of genetic material to a non-homologous chromosome. It results from two breaks of one chromosome release a fragment and one break in another chromosome to insert this fragment  Types of structural abnormalities 7) Translocation: It involves exchange of genetic material between two chromosomes, involving two types: Reciprocal translocation and Robertsonian translocation (centric fusion) ✔ Reciprocal translocation: no loss of genetic material, but an exchange of genetic material between two non-homologous chromosomes to form two derivative chromosomes.  Types of structural abnormalities ✔ Reciprocal translocation: e.g. balanced reciprocal translocation between a chromosome 3 and a chromosome 17 G-banding karyotype of 46, XX, t (3q;17q)  Types of structural abnormalities ✔ Robertsonian translocation (centric fusion) It results from break at or near the centromere in two acrocentric chromosomes (D/D, D/G, G/G) and subsequent fusion of their long arms. The fragment formed by fusion of their short arms is lost. It is a functionally balanced translocation though chromosome number is reduced 45. carriers are normal because of two short arms that lost do not carry important genetic material.  Types of structural abnormalities ✔ Robertsonian translocation (centric fusion): Normal carrier G-banding karyotype of 45,XX,-14,-21,+t(14q21q) Normal carrier Types of structural abnormalities ✔ Robertsonian translocation (centric fusion) How can normal carrier produce Down syndrome?  Types of structural abnormalities ✔ Robertsonian translocation (centric fusion) How can normal carrier produce Down syndrome? G-banding karyotype of 46,XY,-14,+rob(14q21q) G-banding karyotype of 45,XX,-14,-21,+t(14q21q) (Down Syndrome) Normal carrier Structural Chromosomal Abnormalities ❖ The deletions, ring chromosomes and ischromosomes are always unbalanced. ❖ The inversions, insertion, reciprocal translocations and Robertsonian translocations may be balanced or unbalanced. Karyotype nomenclature ✔ Normal female or male: 46, XX or 46,XY ✔ The plus (+) or minus (-) sign followed by a number indicate an extra or missing entire chromosome: e.g.47,XX,+21 or 45, XX, -15 ✔ When a piece of a chromosome is missing the chromosome number is indicated followed by a ‘p’ or ‘q’ and a minus (-) sign: e.g. 5p- ✔ Other notations include ‘del’ (deletion), ‘dup’ (duplication), ‘inv’ (inversion), ‘ins’ (insertion), ‘s’ (satellite), ‘rob’ (Robertsonian translocation ) and ‘t’ (translocation) Different unknown structural chromosomal abnormalities Detecting by chromosome painting