Information on Genes

Distinguishing full siblings from half siblings

2009-06-22T17:30:00.011-04:00

Can you determine if three sisters have the same father by DNA testing of the three sisters?

This is a question about the availability of genetic tests that distinguish full siblings (such as sisters with the same mother and father) from half siblings (such as sisters with the same mother but different fathers). Although full siblings, like parent-child pairs, share half of their alleles, the analysis is a bit trickier. Consider these examples:
The numbers here represents the allelic state of one marker. Each child inherits one allele (one version of the marker) from each parent. In this example, Amy has inherited allele 1 from her father and allele 3 from her mother. Because children must share one allele with each of their parents it is relatively easy to rule out paternity. For example, P2 cannot be Brooke's father because he has completely different alleles from her (1 and 5 vs. 2 and 3). Unlike parents and their children, full siblings can have completely different alleles (e.g. Amy and Casey). Since the question refers to three sisters, it would be possible to rule out all three having the same father (e.g. sisters with genotype 1/3 (Amy), 2/3 (Brooke) and 5/3 (Dawn) cannot all be full sisters because there are three different alleles in combination with the 3, and a single parent can only contribute two possible alleles). However, this is not always the case, and it is even possible for half-sisters to have the same genotype at any one marker (e.g. Amy and Erin) because any two possible fathers could share one or two alleles by chance.

Thus, distinguishing full-siblings from half-siblings comes down to statistics, and "results" are reported as probabilities. Since that is the case, the more markers the better. Many of the genetic testing services probably aren't using enough markers (but they do provide guidance as to how (un)reliable their result is). On the other hand, a full genotyping service, like 23andme, which uses thousands of markers, would provide a reliable result. So, the bottom line is yes, you can determine, with confidence, whether three sisters have the same father by testing the sisters. However, you need to use a lot of markers to do it, and most genetics testing companies probably don't use enough. If you're going to have the testing done, ask the testing service how many markers they use.

What's the best source for information about specific genes?

2009-04-10T16:24:00.008-04:00

We are interested in studying gene expressions in living animals, by means of different in-vivo and in-vitro imaging techniques. We also plan to execute tests on living organisms by using Affymetrix or Navigenics or equivalent DNA microarray test chips, but we know that interpretation of such tests are closely related to the ability to execute reliable and effective reannotation vs. existing validated databases of identified genes. We know that services provided by Affymetrix often provide little informative annotation for most known genes (identified as "transcribed locus"), and we would like to know if anyone in the world can provide an effective reannotation service using our DNA microarray test files, i.e. by executing rigorous tests of our Affymetrix chip probeset sequences against all currently available transcript sequences in latest database releases.

This is a question about gene annotation. I think it's really about how to attach a small bit of truly useful information to many genes in a list. The specific question seems to concern Affymetrix data files in particular.

A list of standard sources for information about human genes follows (in most cases I provide a sample link to the page for CFTR). Entries in these databases are extensively linked to each other.

OMIM, Online Mendelian Inheritance in Man. (CFTR)
Entrez Gene, NCBI's searchable database of genes from RefSeq genomes. (CFTR)
GeneCards, a searchable, integrated database of human genes.(CFTR)
HGNC, HUGO gene nomenclature committee, (CFTR)
Ensembl, genome databases for vertebrates and other eukaryotic species. (CFTR)
Ensembl's BioMart tool may be one answer to this question).
GeneWiki, Wikipedia's gene pages. (CFTR; HBB)

How quickly does inbreeding produce homozygosity?

2008-01-05T13:47:00.000-05:00

What is the probability that locus is homozygous due to inbreeding after a given number of generations? The answer should be an equation expressing this probability as a function of the number of generations.

This question was inspired by a recent review of mouse genetics (Peters et al. 2007. "The mouse as a model for human biology: a resource guide for complex trait analysis" Nature Reviews Genetics 8, 58-69. doi:10.1038/nrg2025), which states, without qualification, that "Inbred mouse strains are derived from a single parental mating pair with subsequent repeated brother–sister intercrosses and no breeding from non-sibling mice. After 20 generations of inbreeding, the mice are genetically identical and homozygous at all loci." 20 generations is an accepted benchmark that leaves a very low probability of homozygosity, but that probability is not zero. What is it?

This is really three questions (or more).

1) Selfing organisms like Arabidopsis thaliana or Caenorhabditis elegans present a simple case. Here, the probability that a given locus remains heterozygous is simply (1/2)ⁿ, where n is the number of generations.

2) The mouse, which represents all diploid species where crosses between full siblings is possible. Brothers and sisters that share the same two parents. I suspect the equation for this case has been worked out. What is the answer?

3) Species where females store sperm. In this case one can isolate a female each generation. She will have mated with her (possibly half-) brothers prior to isolation. Here the probability of homozygosity is a function not only of the number of generations, but also the probability of the female having mated with a full brother vs. a half-brother.

What do we really know about earlobe genetics?

2007-11-28T14:11:00.000-05:00

My husband and I both have attached earlobes. Our newly born son has detached earlobes. How is this possible since attached earlobes are recessive?

- Curious

That is a great question. Many of us learned in high school that attached earlobes are recessive, and it is easy to find that information repeated on the web as an illustration of dominance patterns. An example is the detailed treatment at the Singapore Science Center, which explores various possible parental combinations and concludes that "if both parents were homozygous recessive, they could not have a child with the dominant allele." That is certainly true, and it seems to make a liar out of Curious. Was her child switched in hospital? Should Curious become Alarmed or Suspicious?

I don't think so. I could not find the source of the "fact" that attached earlobes are recessive. I consulted OMIM (the Online Mendelian Inheritance in Man), and they have very little (OMIM 128900). What they do have calls into question the assumption that "attached earlobes are recessive."

Free earlobes are dominant in the view of some. Dutta and Ganguly (1965) suggested polygenic inheritance. There is a variety that is perhaps better classified as 'lobeless' than 'attached.' Lai and Walsh (1966) concluded that 'a simple Mendelian gene effect is unlikely to be responsible for the earlobe types.'

The other issue raised here is whether or not free earlobes is even a bivariate trait (in which case everyone's earlobes could be categorized as either attached or detached). That is necessary for simple dominance to make sense. In the words of students from Willowbrook high school who did a study of this, "it's harder to tell earlobes, so the count on these could be less accurate." OMIM states that "there is a variety that is perhaps better classified as 'lobeless' than 'attached.'" Different forms might show different patterns of inheritance.

I suspect that this, along with a large number of ordinary traits, will be examined anew in the era of personal genomics. For example, the people at deCODE genetics just published a report on the genetics of hair and skin pigmentation (Sulem et al., 2007: Nature Genetics 39:1443, PMID 17952075). Perhaps earlobes will be next.

This question may be most important as a cautionary tale about genetics education. Teaching students about earlobes seems very innocent, but this case illustrates why oversimplification might not be prudent.

What ancestry companies provide actual genetic data?

2007-11-25T13:34:00.000-05:00

This question is inspired by an article in today's New York Times business section ("DNA Tests Find Branches but Few Roots"). The article is nice in that it compares the cost of ancestry testing by various companies, shows that results differ, and quotes Henry Louis Gates Jr. making reasoned assessments of the role that DNA testing can play. However, the article fails to say which companies provide customers with the raw genotype information that they can use to make their own assessments as more information becomes publicly available.

This map (from the article) shows the results returned to the author (Ron Nixon) from five different companies. Presumably, the actual genetic information they gathered is a bit less variable than their interpretation. If I paid to have my DNA analyzed, I would want the actual data so that I could make my own interpretations using the best information available from all sources.

The article lists 20 companies that will test your DNA for the purpose of learning about ancestry. Can anyone tell us which ones provide the client with the actual information (sequence or polymorphism data) that can be compared with published genetic demographic data?

Is race "real"?

2007-11-18T01:13:00.000-05:00

Someone wrote in "wondering what the current stance is with geneticist in regards to whether different human races exist or not." This important question has been discussed at length already, and I refer readers to a Social Sciences Research Council forum on race, the special issue of Nature Genetics on race published in November of 2004, and an edited volume by Jefferson Fish. I side with those who feel that race, as it is normally understood, is a social construct. Those biological definitions that might be partially valid for humans differ significantly from the way the concept is normally used in our society. However, others argue for the importance of considering "ethnicity" in clinical trial design (Taylor et al. 2005), and the drug BiDil has been licensed exclusively for African-Americans (for a recent news report in "The Times" click here).

So, my answer to this questions has been given before.

It seems to me that if a drug differs in either safety or efficacy for one "race" or another, then the underlying basis is probably either a genetic difference or a cultural difference. In the first case, the relevant genetic difference itself, or a related biomarker, would be much more reliable than popular notions of race. On the other hand, if the basis is cultural, the relevant practice (such as lifestyle or diet) should be identified. I was therefore gratified to see Nature Genetics publish this letter from Jonathan Kahn making the case against the misuse of race, as well as a sidebar showing how the media has misrepresented their own statements.

However, additional answers are welcomed.

What can I learn about my ancestors from my DNA?

2007-11-17T14:00:00.000-05:00

What can I learn about my ancestors from my DNA? What companies provide this information? How much does it cost? What exactly do I learn?

How does this site work?

2007-11-16T23:04:00.000-05:00

This site, "Information on Genes" (ongenes.com) is a place where answers to questions on genes, genetics and genomics are provided by experts in the field.

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