Direct detection of null alleles in SNP genotyping data

Human Molecular Genetics
Christopher S CarlsonDeborah A Nickerson

Abstract

Pinpointing genetic associations in the human genome relies heavily on the accuracy of the underlying genotype data. Null alleles can generate significant inaccuracies in genotype data and can negatively affect the statistical power of a study. Existing quality control (QC) tests, including tests of Hardy-Weinberg equilibrium, are not sensitive enough to detect the presence of even moderately frequent null alleles in the data. We show that direct analysis of raw data from a quantitative genotyping platform can detect up to 75% of null alleles, even at frequencies below the sensitivity of more traditional methods. Detecting unexpected null alleles not only has benefits in QC of genotype data but may also be valuable in detecting rare, functional null alleles that would otherwise be missed.

References

Oct 11, 1994·Nucleic Acids Research·T T NikiforovM R Knapp
May 16, 1998·Genome Research·D GordonP Green
Mar 20, 1999·Genetic Analysis : Biomolecular Engineering·K J Livak
Mar 20, 1999·Genetic Analysis : Biomolecular Engineering·R J SapolskyJ B Fan
May 13, 1999·Nature Genetics·M J RiederD A Nickerson
Jun 20, 2002·Human Genetics·Nadine NortonMichael C O'Donovan
Apr 5, 2003·Annals of Human Genetics·K M Rice, P Holmans
Dec 19, 2003·American Journal of Human Genetics·Christopher S CarlsonDeborah A Nickerson
Jan 30, 2004·Genetic Epidemiology·Sun Jung KangStephen J Finch
Jul 9, 2004·Human Molecular Genetics·Stephen J SawcerJonathan L Haines
Jul 13, 2004·Nature Genetics·David FredmanAnthony J Brookes
Sep 2, 2004·Cold Spring Harbor Symposia on Quantitative Biology·J B FanM S Chee
Mar 23, 2005·Nature Methods·Hajime MatsuzakiRui Mei
Apr 15, 2005·Mutation Research·Richard ShenArnold Oliphant
May 27, 2005·American Journal of Human Genetics·Andrew J SharpEvan E Eichler
Aug 16, 2005·Methods in Molecular Biology·Ming Xiao, Pui-Yan Kwok
Nov 30, 2005·Nucleic Acids Research·Yuker WangMalek Faham
Dec 6, 2005·Nature Genetics·Donald F ConradJonathan K Pritchard
Dec 6, 2005·Nature Genetics·David A HindsKelly A Frazer
Feb 10, 2006·Nature Genetics·Steven A McCarrollUNKNOWN International HapMap Consortium
Feb 25, 2006·Human Molecular Genetics·Tera L NewmanEvan E Eichler

❮ Previous
Next ❯

Citations

May 16, 2009·Current Opinion in Pediatrics·David M Walker
Jan 15, 2011·Current Protocols in Human Genetics·Stephen TurnerMarylyn D Ritchie
Jun 6, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Claudia HüebnerLynnette R Ferguson
Jun 4, 2008·American Journal of Human Genetics·Lude FrankeCisca Wijmenga

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.