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History of genetic disease

Down syndrome and genetics — a case of linked histories

Nature Reviews Genetics volume 6, pages 137–147 (2005)Cite this article

Abstract

Down syndrome, the most common genetic cause of intellectual disabilities, was first described in 1866, during an era of great change in our understanding of genetics and evolution. Because of its importance, the history of research on Down syndrome parallels the history of human genetics. In many instances, research on Down syndrome has inspired progress in human genetics. In this article, we describe the interplay between advances in the understanding of genetics and the understanding of Down syndrome from its initial description to the present, and on the basis of this historical perspective, speculate briefly about the future of research on Down syndrome.

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Figure 1: Systems biology or the study of “complex webs of biochemical processes”.

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Acknowledgements

The authors would like to acknowledge the support of the US National Institutes of Health, the Jerome Legeune Foundation, the Bonfils–Stanton Foundation, the Boettcher Foundation, the Denver Foundation and the Alvin Itkin Foundation.

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Authors and Affiliations

  1. Eleanor Roosevelt Institute and the Department of Biological Sciences at the University of Denver and also at the Department of Psychiatry, University of Colorado Health Sciences Center, 1899 Gaylord Street, Denver, 80206, Colorado, USA

    David Patterson & Alberto C. S. Costa

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  1. David Patterson
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Correspondence to David Patterson.

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DATABASES

Entrez

APP

IFNAR1

SOD1

GARS

HPRT

Pfkl

Dyrk1a

Sim2

S100β

Ets2

OMIM

Down syndrome

Alzheimer disease

Acute myeloid leukaemia

Glossary

ACROCENTRIC CHROMOSOME

A chromosome in which the centromere is near to one end, as in human chromosomes 13–15, 21, 22 and Y. All mouse chromosomes are acrocentric.

ACUTE MYELOID LEUKAEMIA

A cancerous overproduction of immature myeloid white blood cells (blast cells).

ANEUPLOID

Having an abnormal number of chromosomes that are not an exact multiple of the haploid number. The antonym is euploid.

CHOLINERGIC MARKERS

These are biochemical or immunological markers for cholinergic neurons (presynaptic neurons that produce acetylcholine). Although it remains controversial, it has been suggested that loss of function of basal forebrain cholinergic neurons might be linked to neurodegenerative changes in the cerebral cortex of individuals with Alzheimer disease and Down syndrome (the so-called cholinergic hypothesis).

CpG ISLAND

A genomic region of about one kilobase that has more than 50% C+G content.

CRANIOFACIAL DYSMORPHOGENESIS

Abnormal development of the bones of the skull, including the facial bones.

DIFFERENCE GEL ELECTROPHORESIS

A technique whereby two or more protein samples are labelled with different fluorescent dyes so that they can be mixed together, co-separated and visualized on a single 2D gel.

DUODENAL ATRESIA

A condition in which the duodenum (the first part of the small bowel) has not developed properly and does not allow the passage of stomach contents.

ENDOSOME

A vesicle formed by invagination of the plasma membrane.

FOETAL NUCHAL TRANSLUCENCY

The appearance on ultrasound examination of a subcutaneous collection of fluid behind the foetal neck.

HAPLOTYPE BLOCKS

The apparent haplotypic structure of the recombining portions of the genome, in which sets of consecutive co-inherited alleles are separated by short boundaries. There is debate about the origins of haplotype blocks and whether the boundaries correspond to recombination hotspots.

HYPERTHYROIDISM

An abnormality of the thyroid gland in which secretion of the thyroid hormone is increased and not regulated properly.

MASS SPECTROMETRY

A technique in which molecules are ionized, the ions are separated in the gaseous state and the ratio of mass to charge is determined to derive structural information. This technique requires only a small amount of sample.

MYELODYSPLASTIC SYNDROME

A condition in which the bone marrow cannot produce blood cells effectively; many of the blood cells that are formed are defective, which results in low blood cell counts.

POSITRON EMISSION TOMOGRAPHY

(PET). Imaging of the emission of positrons from the brain after a small amount of radioactive isotopes have been injected into the blood stream to routinely and quantitatively measure metabolic, biochemical and functional activity in living tissue.

REAL-TIME PCR

A technique designed to detect and quantify sequence-specific PCR products as they accumulate in 'real-time' during the PCR amplification process.

SYNTENIC REGIONS

A genomic region that is collinear in the order of genes (or of other DNA sequences) in a chromosomal region of two species.

TWO-DIMENSIONAL GEL ELECTROPHORESIS

A gel electrophoresis method in which a protein sample is separated by isoelectric point in one dimension and by size in a second, perpendicular dimension.

WHOLE-GENOME ASSOCIATION STUDIES

A set of methods that are used to correlate polymorphisms in genotype to polymorphisms in phenotype in populations on a genome-wide scale.

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Patterson, D., Costa, A. Down syndrome and genetics — a case of linked histories. Nat Rev Genet 6, 137–147 (2005). https://doi.org/10.1038/nrg1525

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