Triple repeat or trinucleotide repeat disorders: A trinucleotide or triple repeat is a sequence of three DNA nucleotides that is repeated a number of times in a row. DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. In some instances, the number of triplet repeats in a given gene increases (expands) from generation to generation until some threshold is passed that results in disease.
Anticipation: Disease tends to manifest earlier and in a more severe form with each succeeding generation. Occurs due to expansion in the number of trinucleotide repeats.
| Disorder | Associated triple repeat |
| Huntington’s disease, spinocerebellar ataxia types 1-3,6,7 | CAG |
| Fragile X syndrome | CGG |
| Friedreich’s ataxia | GAA |
| Myotonic dystrophy | CTG |
Genomic imprinting: Normally, of two copies of each autosome in our cells, one is of paternal while the other is of maternal origin. Usually both copies of each gene are active, or “turned on,” in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin, some genes are normally active only when they are inherited from a person’s father, others are active only when inherited from a person’s mother. This phenomenon is known as genomic imprinting. The inactive gene is methylated. Genomic imprinting normally occurs in a small percentage of human genes only.
Uniparental disomy occurs when both copies of a chromosome are received from one parent while no copies are received from the other parent. When uniparental disomy affects a gene that normally undergoes genomic imprinting, then it may cause disease as such a person will lack a set of genes needed for cellular function.
Prader-Willi syndrome: Gene on paternal chromosome 15 is deleted/imprinted or maternal uniparental disomy; hypotonia, hyperphagia, increased appetite, obesity, mental retardation, temper tantrums, almond shaped eyes, small hands and feet, light hair, unusually fair skin, infertility
Angelman syndrome: Gene on maternal chromosome 15 is deleted or imprinted, mutated or paternal uniparental disomy occurs. Developmental delays, mental retardation, ataxia, speech defects, seizures, microcephaly, happy smiling child, hand flapping, hyperactivity, scoliosis
Beckwith-Wiedemann syndrome: Abnormal imprinting at 11p15. Overgrowth, macrosomia, asymmetric growth, omphalocele, umbilical hernia, macroglossia, visceromegaly, hypoglycemia, Wilms tumor, hepatoblastoma, AD
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