Lesson 10 - Chromosomal Aberrations (Structural) PDF

CYTOGENETICS TERM NATIONAL UNIVERSITY MANILA — BACHELOR OF SCIENCE IN MEDICAL TECHNOLOGY SECOND YR – FINALS | MLSCYGEN | MR. KIAN ESTEBAN RMT, MSMT, MD, MPH, DIPSUI...

CYTOGENETICS TERM NATIONAL UNIVERSITY MANILA — BACHELOR OF SCIENCE IN MEDICAL TECHNOLOGY SECOND YR – FINALS | MLSCYGEN | MR. KIAN ESTEBAN RMT, MSMT, MD, MPH, DIPSUI 01 LESSON 10: CHROMOSOMAL ABERRATIONS (STRUCTURAL) OUTLINE STRUCTURAL ABNORMALITIES Cytogenetic Notation Result from breakage of a chromosome region with loss or Structural Abnormalities subsequent rejoining in an abnormal combination Structural Rearrangements 2 General types 1. Balanced rearrangements – no loss or gain of genetic chromatin CYTOGENETIC NOTATION 2. Imbalanced rearrangement – gain or loss of genetic material BALANCED REARRANGEMENTS Change the chromosomal gene order but do not remove or duplicate any of the DNA of the chromosomes IMBALANCED REARRANGEMENT Change the gene dosage of a part of the affected chromosomes STRUCTURAL ABERRATIONS HAPPEN DUE TO: Errors during meiosis Errors during mitosis Exposure to substances that cause birth defects (teratogens) STRUCTURAL REARRANGEMENTS 1. Inversions 2. Deletions 3. Ring formations INTERNATIONAL SYSTEM FOR HUMAN 4. Duplications CYTOGENETIC NOMENCLATURE (ISCN) Each area of chromosome given 5. Isochromosomes number 6. Insertions Lowest number closest (proximal) to 7. Translocations centromere Highest number at tips (distal) to 1. INVERSIONS A segment of a centromere chromosome is reversed end to end Occurs when a single chromosome undergoes breakage and rearrangement within itself Can be inherited or it may be a mutation that appears in a child whose family has no history Type of mutation where a sequence of nucleotides in the DNA is reversed or inverted Sometimes inversions are visible in the structure of the chromosomes 1|L e g a s p i , E r i c a & Ch a n g , P a u l  CHROMOSOMAL ABERRATIONS (STRUCTURAL) TYPES OF INVERSIONS TERMINAL DELETIONS Pericentric Inversions Loss of chromosomal material Paracentric Inversions from the end of a chromosome PERICENTRIC INVERSION Chromosomal inversion that involves the centromere CRI-DU-CHAT SYNDROME Cat-cry syndrome, 5P minus syndrome and Lejeune’s syndrome First described by Jérôme PARACENTRIC INVERSION Lejeune in 1963 Chromosomal inversion that does Deletion of certain genes on not include the centromere chromosome 5 Deleted genes: o HTERT gene -> DNA functioning o CTNND2 gene -> Cell adhesion, Cell movement, Active in NS FEATURES: CRI-DU-CHAT SYNDROME High-pitched, cat-like cry or weak cry CHROMOSOME 9 INVERSION Low birth weight One of the most common structural balanced chromosomal Small head -> microcephaly variants Rounded face Broad, flattened bridge of the nose Some cases it is associated with: Eyes spaced wide apart Congenital anomalies Folds of skin over the eyelids Growth retardation Abnormalities of the palate Infertility Small chin Recurrent pregnancy loss Malformations of the ears Cancer 2. DELETIONS A part of a chromosome is missing or deleted Interstitial deletion Terminal deletion INTERSTITIAL DELETION Arise after two breaks in the same chromosome arm WOLF-HIRSCHHORN SYNDROME and loss of the First described by Hirschhorn and Cooper in 1961 segment between Deletion of the distal short arm of chromosome 4 the breaks Deleted genes NSD2 -> distinctive facial appearance and developmental delay LETM1-> seizures or other abnormal electrical activity in the brain MSX1 -> dental abnormalities and cleft lip and/or palate 2|L e g a s p i , E r i c a & C h a n g , P a u l  CHROMOSOMAL ABERRATIONS (STRUCTURAL) FEATURES: WOLF-HIRSCHHORN SYNDROME Distinctive facial features ❖ Broad, flat nasal bridge and a high forehead ❖ Greek warrior helmet FEATURES: ANGELMAN SYNDROME Delayed growth and development Developmental delay Motor skills such as sitting, standing, and walking are Movement or balance disorder significantly delayed Behavioral uniqueness Speech impairment GENOMIC IMPRINTING Normal form of gene regulation that causes a subset of UNIPARENTAL DISOMY genes to be expressed from one of the two parental 2 copies of a chromosome come from the same parent chromosomes Most genes -> Inherit working copies o One form mother, other from father Imprinting -> Inherit one working copy o Either from paternal or maternal o Epigenetically silenced o Silencing occurring through addition of methyl groups during egg/sperm formation -> DNA Methylation PRADER-WILLI SYNDROME H19 gene is an First described in 1956 by imprinted gene Swiss doctors o Prof. A Prader, Dr A expressed only from the maternal Labhart, and Dr H chromosome 11. Willi Igf2 (insulin-like Occurs as the result of growth factor 2 )is absence of expression of paternal genes from an imprinted gene, being expressed chromosome 15q11-q13 only from the paternal chromosome 11. ANGELMAN SYNDROME Mutation in UBE3A gene in maternal chromosome 15 (q12) o ubiquitin protein ligase Absence of chromosome Hypotonia region 15 (15q11-q13) Hypogonadism Named after Harry Angelman Obesity who first described the CNS and Endocrine gland syndrome in 1965 dysfunction 3|L e g a s p i , E r i c a & C h a n g , P a u l  CHROMOSOMAL ABERRATIONS (STRUCTURAL) RING CHROMOSOMES TRANSLOCATIONS Double strand breaks -> Result from breakage & reunion Breakage in two chromosomes and each of the broken of a single chromosome with loss of chromosomal material pieces reunites with another chromosome outside the break points Balanced translocation - If chromatin is neither lost nor Telomere dysfunction -> One or both telomeres may join gained the exchange to form a ring chromosome without significant loss of Unbalanced translocation - loss or gain of chromatin chromosomal material material results in partial monosomy or trisomy for a segment of the chromosome Ring chromosome 14 syndrome: r(14) DUPLICATION Partial trisomy for part of a chromosome This can result from an unbalanced ROBERTSONIAN TRANSLOCATION insertion or unequal crossing over in Centric Fusion meiosis or mitosis Translocation in which the centromeres of two acrocentric chromosomes fuse to generate one large chromosome ISOCHROMOSOMES Arise from either abnormal division of the centromeres Horizontal division Each resulting daughter cell has a chromosome in which the short arm or the long arm is duplicated INSERTIONS Involve movement of a segment of a chromosome from one location to another location of the same chromosome or to another chromosome. 4|L e g a s p i , E r i c a & C h a n g , P a u l