Cytogenetics
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
A karyotype is a set of chromosomes from one cell. There are 46 chromosomes occurring in 23 pairs (Figure 6.1). Chromosomes are distinct bodies found in the nucleus of cells, best visible in the phase of the cell cycle called metaphase. Chromosomes are composed of protein and DNA, and hold the genetic information in the form of linear sequences of four bases (A, T, C, and G). The DNA sequence for a single trait is called a gene. Each chromosome contains a few thousand genes, which range in size from a few thousand bases up to 2 million bases. The first 22 pairs are labeled longest to shortest. The last pair are called the sex chromosomes, which are labeled X or Y. Females have two X chromosomes (XX), and males have an X and a Y chromosome (XY). Each chromosome has a short or p (petit) arm and long or q (next letter in the alphabet) arm, which are separated by a region known as the centromere. The centromere is a condensed part of chromosome that binds together two sister chromatids and constitutes the attachment site for spindle fiber during cell division. Types of chromosomes are presented in Figure 6.2. Each chromosome arm is further defined by numbering the bands (light and dark bands visible under the microscope after staining with various dyes); the higher the number, the further the area is from the centromere. The band width and the order of bands are specific for each chromosome and allow their identification.
Initial investigation of the infertile couple
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
Males having abnormal spermatogenesis related to testicular failure, such as in NOA or severe oligozoospermia (<5 million/mL), are at increased risk for having genetic abnormalities compared to fertile men (5,88). Genetic testing including karyotype analysis and Y-chromosome microdeletion is recommended in these circumstances before performing ICSI (5). A karyotype analysis can diagnose numeric chromosomal abnormalities (e.g., Klinefelter’s syndrome [KS]) or other chromosomal structure abnormalities (e.g., Robertsonian or reciprocal translocations). KS is the most common chromosomal abnormality: Non-mosaic KS accounts for 11% of azoospermia cases and mosaic KS accounts for 0.5% of severe oligozoospermia cases (89). If the karyotype is abnormal, there is an increased risk of sperm chromosomal aneuploidy, and genetic counseling including preimplantation genetic diagnosis should be discussed with the couples prior to assisted reproduction.
Genetic and genomic investigations
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
The first genetic investigation used in clinical practice was the karyotype, as already described in Chapter 4. The visual inspection of the full set of Giemsa-stained (banded) chromosomes from cells caught in an arrested mitosis, using the light microscope, allows the recognition of (large) deletions or duplications and other structural rearrangements. When the microscope image is photographed, so that the chromosomes can be neatly arranged into their pairs, we describe this display as the karyotype. This is likely to remain a standard investigation in genetics for many years but only for a restricted set of contexts, where a structural rearrangement of the chromosomes is likely or where such a rearrangement is known to be present in the family and a relative seeks cascade testing, to see if they have inherited the rearrangement. Other applications of the karyotype are being superseded by molecular investigations; in fact, the distinction between the cytogenetics and the molecular genetics laboratory is disappearing as ‘molecular’ methods are now often used to answer ‘cytogenetic’ questions.
Developments in diagnosis and treatment of essential thrombocythemia
Published in Expert Review of Hematology, 2019
Barbara Mora, Francesco Passamonti
Mora et al. [147] focused on cytogenetic data available on the whole MYSEC cohort of post PV (PPV) and PET MF at the time of diagnosis (376 cases, of whom 188 PET MF, 188 PPV MF). Abnormal karyotype was found in 128 (34%) patients. Within chromosomal abnormalities, 72 (56%) were a sole abnormality, 26 (20%) complex karyotype (of which 11 −8.5%- were monosomal), 22 (17%) double abnormalities and eight abnormal karyotypes not further specified [147]. Among the sole abnormalities, the most prevalent were: 20q- (18 cases, 25%), 13q- (15 cases, 21%), +8 (6 cases, 8%) and +9 (4 cases, 6%). Other individual alterations were present in less than 5% of patients [147]. Abnormal karyotype conferred a more advanced clinical phenotype. Median survival was significantly different between normal and abnormal karyotype and estimated at 10.1 years (95% CI: 8.1-not reached-NR-) and 6.1 years (95% CI: 4.8-NR), respectively (P = .012) [147]. Post-hoc log-rank tests comparing the effect of different cytogenetic abnormalities found that patients with monosomal, those with complex karyotype without monosomal and those with complex karyotype had worse survival, with a median estimate of 2.1 years (95% CI: 1-NR), 3.4 years (95% CI: 2.6-NR), and 2.7 years (95% CI: 2-NR), respectively [147]. All groups had inferior survival when compared to normal karyotype, sole or double abnormalities (P< .001) [147].
Clarifying the Blurry Boundaries between Research and Clinical Care
Published in The American Journal of Bioethics, 2022
Forough Noohi, Lainie F. Ross
Good ethics begins with good facts, and methodology matters. We are told that the researchers diagnosed Klinefelter Syndrome by genomic sequencing in a non-CLIA lab. CLIA regulations were designed to reduce failures of labeling and specimen identification (CDC 2022). Returning research results from a non-CLIA lab raises issues of sample labeling accuracy. Also significant is how the diagnosis was made. We do not know if the researchers conducted formal karyotyping after identifying Klinefelter Syndrome with sequencing. The majority of karyotypes detected in Klinefelter Syndrome individuals are 47,XXY while others are non-mosaic (e.g., 48,XXXY) or mosaic aneuploidy (i.e., 46,XY/47,XXY). Karyotyping is necessary to determine whether the participant is a mosaic (which often has milder symptoms) (Matsumoto and Anawalt 2019). This may tip the scales of risks and benefits in deciding whether the finding is “urgently important.”
A new compound heterozygous mutation in a female with 17α-hydroxylase/17,20-lyase deficiency, slipped capital femoral epiphysis, and adrenal myelolipoma
Published in Gynecological Endocrinology, 2019
Fan Yang, Yongting Zhao, Jie Lv, Xia Sheng, Lihong Wang
The chromosome karyotype was 46, XX. Transrectal ultrasonography showed a primordial uterus (1.9 × 1.8 × 1.4 cm3), and both ovaries were absent. The adrenal computed tomography (CT) showed mixed density in the bilateral adrenals. The maximum diameter of the section was 123 mm and the CT value was −77–13 Hu (Figure 1(F)). AML was considered based on the imaging examinations. However, the patient refused further pathological biopsy or surgical treatment. The bone mineral density examination of the lumbar spine was suggestive of severe osteoporosis (less than −2.5 SD). The relevant hormone results are shown in Table 1. Luteinizing hormone and follicle-stimulating hormone levels were elevated. Testosterone and estradiol levels were extremely low. The ACTH level was elevated, and the level of cortisol was reduced. Notably, the plasma concentrations of progesterone were elevated, while the levels of 17-hydroxyprogesterone and androstenedione were markedly low. The aldosterone level was normal, and plasma renin activity was significantly repressed. According to the manifestations and these results, a diagnosis of 17-OHD was suspected.
Related Knowledge Centers
- Centromere
- Chromatid
- Microscope
- Microscopy
- Cell Cycle
- Metaphase
- Chromosome
- Species
- Photography
- Micrograph