The two sides of chromosomal instability: drivers and brakes in cancer

Karyotyping For Chromosomal Abnormalities

In order to maximize the diagnostic information obtained from a chromosome preparation, images of the individual chromosomes are arranged into a standardized format known as a karyotype, or more precisely, a karyogram (Figure 1a-c). According to international conventions, human autosomes, or non-sex chromosomes, are numbered from 1 to 22, in descending order by size, with the exceptions of chromosomes 21 and 22, the former actually being the smallest autosome. The sex chromosomes are generally placed at the end of a karyogram.

Within a karyogram, chromosomes are aligned along a horizontal axis shared by their centromeres. Individual chromosomes are always depicted with their short p arms—p for "petite," the French word for "small"—at the top, and their long q arms—q for "queue"—at the bottom. Centromere placement can also be used to identify the gross morphology, or shape, of chromosomes. For example, metacentric chromosomes, such as chromosomes 1, 3, and 16, have p and q arms of nearly equal lengths. Submetacentric chromosomes, such as chromosomes 2, 6, and 10, have centromeres slightly displaced from the center. Acrocentric chromosomes, such as chromosomes 14, 15, and 21, have centromeres located near their ends.

Arranging chromosomes into a karyogram can simplify the identification of any abnormalities. Note that the banding patterns between the two chromosome copies, or homologues, of any autosome are nearly identical. Some subtle differences between the homologues of a given chromosome can be attributed to natural structural variability among individuals. Occasionally, technical artifacts associated with the processing of chromosomes will also generate apparent differences between the two homologues, but these artifacts can be identified by analyzing 15–20 metaphase spreads from one individual. It is highly unlikely that the same technical artifact would occur repeatedly in a given specimen.

Diagnosing Down Syndrome, Cystic Fibrosis, Tay-Sachs Disease And Other Genetic Disorders

Sometimes, a pediatrician will suspect that a child has a genetic disorder based on the child's symptoms or on the presence of dysmorphic features. For example, if a child has coarse facial features and developmental delays, a pediatrician may have reason to believe that the child has a form of mucopolysaccharidosis. Mucopolysaccharidosis is a family of diseases caused by an enzyme deficiency that leads to the accumulation of glycosaminoglycans (GAGs) within the lysosomes of cells. In one particular variant of this disease known as mucopolysaccharidosis I (MPS I), a deficiency of the enzyme alpha-L-iduronidase causes a build up of GAGs in tissues and organs, which in turn leads to a host of signs including skeletal deformities, coarse facial features, enlarged liver and spleen, and mental deficiencies. Because of the progressive nature of MPS I, a child might not exhibit noticeable symptoms until one to three years of age or even later, depending on severity.

There are a number of reasons that a pediatrician might refer a child to see a geneticist. Geneticists can confirm or rule out a physician's diagnosis based on the findings of a physical exam and various tests. In the case of a child with suspected MPS, if the enzymatic deficiency associated with the disorder is confirmed via testing, DNA analysis may also be performed to determine the exact genetic mutation causing the disorder. Because MPS I is inherited in an autosomal recessive fashion, identification of the mutation can allow the family to undergo carrier screening, as well as prenatal or preimplantation diagnosis in any future children.

Alfie Steele: 'No Abnormalities Which Could Cause Epilepsy'

Isabel Kimbrey

Journalist, BBC Hereford & Worcester

Alfie Steele, 9, was found dead in a bath at his home in Droitwich in February 2021

A boy found dead in a bath did not have genetic abnormalities which would have caused epilepsy or sudden cardiac episodes, a murder trial has heard.

Nine-year-old Alfie Steele was discovered at his home in Droitwich, Worcestershire, in February 2021.

His mother, Carla Scott, 35, and her partner, Dirk Howell, 41, deny murder.

Dr Ian Ellis told Coventry Crown Court on Friday he had found an abnormality in one of Alfie's chromosomes which may have caused developmental delays.

Although there is limited scientific evidence, Dr Ellis explained that children with this abnormality tended to suffer from conditions such as Autistic Spectrum Disorder, Attention Deficit Hyperactivity Disorder and seizures.

The consultant clinical geneticist told the jury that this same abnormality had also been found in the schoolboy's biological father.

Prosecutor Michelle Heeley KC asked Dr Ellis if there were any genes which could also have been tested to determine if someone had epilepsy.

Dr Ellis said: "Yes, there are a number of genes that carry a high risk of epilepsy.".

Heeley then asked if Alfie and his mother, who the court has previously heard suffered from epilepsy, had also been tested for these genes.

"Yes, but no abnormalities were found", confirmed Dr Ellis.

He explained they had also tested gene panels which were responsible for sudden cardiac episodes but confirmed they had found no abnormalities in either Alfie or his mother.

Boy found dead in bath 'did not have epilepsy'

Dead boy's injuries from 'adult who lost control'

Dead boy's mother looked on as he was shouted at

Boy found dead in bath had 50 injuries, trial hears

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