[01.03b] Principles of Genetics & Overview of Genetic Pathology

46 chromosomes – 22 pairs of autosomes – 2 sex chromosomes

What is the normal human somatic cell karyotype?

Karyotyping

What is the best cytogenetic tool to examine chromosomes?

Metaphase

In karyotyping, at what stage are dividing cells arrested?

47, XY, +21

What is the karyotype notation for Trisomy 21 in a male?

p (petit)

What letter denotes the short arm of a chromosome?

Euploid

What term describes a chromosome number that is an exact multiple of the haploid set (23)?

Aneuploid

What term describes a chromosome number that is not an exact multiple of 23?

Nondisjunction

What is the failure of homologous chromosomes or sister chromatids to separate during cell division called?

Mosaicism

What condition is characterized by two or more populations of cells with different chromosomal complements, arising from a post-fertilization error?

Translocation

What structural chromosomal abnormality involves a segment of one chromosome being transferred to another?

Robertsonian translocation

What specific type of translocation occurs between two acrocentric chromosomes with breaks close to the centromere?

Inversion

What structural chromosomal abnormality involves two breaks within a single chromosome with reincorporation of the inverted segment?

Isochromosome

What structural chromosomal abnormality results from the loss of one arm and duplication of the remaining arm?

Ring Chromosome

What special form of deletion involves the fusion of damaged ends of a chromosome?

Trisomy 21 (Down Syndrome)

What is the most common chromosomal disorder and major cause of intellectual disabilities?

Meiotic nondisjunction

What is responsible for 95% of Trisomy 21 cases?

Maternal age

What factor strongly influences the likelihood of Trisomy 21 due to meiotic nondisjunction?

Robertsonian translocation

What accounts for 4% of Trisomy 21 cases and is familial in origin?

Flat facial profile, oblique palpebral fissures, epicathic folds

Name three characteristic facial features of Trisomy 21.

Congenital Heart Disease (CHD)

What co-morbid condition affects 40% of individuals with Trisomy 21?

FISH (Fluorescence in situ hybridization)

What is the fastest way to diagnose Trisomy 21?

Trisomy 18 (Edward Syndrome)

Which trisomy is characterized by prominent occiput, microcephaly, overlapping fingers, and rockerbottom feet?

Trisomy 13 (Patau Syndrome)

Which trisomy is characterized by microcephaly, cleft lip/palate, polydactyly, and rockerbottom feet, often non-compatible with life?

Chromosome 22q11.2 Deletion Syndrome

What syndrome results from a small deletion on the long arm of chromosome 22 and can cause T-cell immunodeficiency and hypocalcemia?

DiGeorge Syndrome and Velocardiofacial Syndrome

What two previously separate disorders are now known to be caused by 22q11.2 deletion?

CATCH 22 (Cardiac abnormality, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia)

What mnemonic is used for Chromosome 22q11.2 deletion syndrome?

Lyonization (X inactivation)

What peculiar characteristic of sex chromosomes involves the inactivation of all but one X chromosome?

SRY gene

What gene on the Y chromosome determines male sex?

Klinefelter Syndrome

What is the most common cause of hypogonadism in males, characterized by a 47, XXY karyotype?

Reduced spermatogenesis and male infertility

What are important reproductive consequences of Klinefelter Syndrome?

Elongated body, gynecomastia, small atrophic testes

Name three distinctive clinical features of Klinefelter Syndrome.

Turner Syndrome

What is the most common sex chromosome abnormality in females, resulting from complete or partial monosomy of the X chromosome?

Short stature and primary amenorrhea

Name two primary clinical features of Turner Syndrome.

L-sided heart disease (e.g., Preductal Coarctation of the Aorta, Aortic root dilation)

What type of congenital heart disease is common in Turner Syndrome?

Sexual ambiguity

What term describes a disagreement among genetic, gonadal, ductal, and phenotypic sex criteria?

True hermaphrodite

What condition involves the presence of both ovarian and testicular tissue?

Female pseudohermaphrodite

What condition is characterized by the presence of ovaries but male external genitalia?

Fragile X Syndrome

What is the most common genetic cause of intellectual disability among males, caused by trinucleotide repeat mutations?

Oogenesis

During which process does the expansion of trinucleotide repeats occur in Fragile X Syndrome?

Macro-orchidism (large testicles)

What is the most distinctive physical feature of males with Fragile X Syndrome, seen in 90% of cases?

PCR (Polymerase Chain Reaction)

What is the method of choice for diagnosing Fragile X Syndrome?

Toxic gain-of-function

What mechanism causes Fragile X-associated tremor/ataxia syndrome and primary ovarian failure, where the FMR1 gene continues to be transcribed?

Maternal inheritance

What unique inheritance pattern is exhibited by mitochondrial DNA?

Heteroplasmy

What term describes individuals having both wild-type/normal and mutant mitochondrial DNA components?

Leber Hereditary Optic Neuropathy

What neurodegenerative disease causes progressive bilateral loss of central vision, inherited maternally?

Genomic imprinting

What mechanism causes important functional differences between maternal and paternal alleles, leading to disorders like Prader-Willi and Angelman syndromes?

Maternal imprinting

What term describes when the maternal allele is transcriptionally silenced, as seen in Angelman syndrome?

Paternally derived chromosome 15

Deletion of which chromosome and origin is associated with Prader-Willi Syndrome?

Hyperphagia and obesity

What are two profound clinical features of Prader-Willi Syndrome?

Maternally derived chromosome 15

Deletion of which chromosome and origin is associated with Angelman Syndrome, characterized by inappropriate laughter?