微单倍型microhaplotypes
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1.什么是微单倍型？
regions encompassing two to four SNPs with an extent of <200 bp that define multiallelic haplotype loci.【4】
2.微单倍型的应用场景？
2.1 individualization
2.2 ancestry inference
2.3 kinship analysis
2.4 mixture deconvolution
微单倍型的另一个好处是可以对混合物进行定量：
Microhaps have an additional ability: identification of mixtures with the potential to quantify the components, i.e., to disentangle mixtures in a quantitative way. The presence of three or more different sequences at sufficient numbers of reads becomes clear evidence of DNA from more than one person contributing to the sample. With many loci multiplexed and with more loci with four or more haplotypes, the microhaps become powerful markers to identify and quantify components of mixtures. Microhaps with 3 or more common alleles (haplotypes)for one sequence of <200 bp will allow computer software to accurately predict the likelihood and levels of mixture based on observing more than two sequence types
at a locus and the numbers of occurrences of each type.【3】
3.如何选择微单倍型？
effective number of alleles (Ae)
average Ae values of even slightly greater than 3.0【5】Ae大于3.0的微单倍型非常有用 这个值可以作为我们过滤的默认值
the probability of “detecting” a mixture with at least one of n loci as 1-(1–.65625)^n
Paternity Index (PI)
200bp长度(主要取决于测序的read长度read length)
不能是 recombination hot spot
an average heterozygosity of >0.4 （可设置）【4】
informativeness (In)
higher In values indicate that a microhap locus has alleles that are frequent in certain
populations and rare in others4.如何评价微单倍型？
random match Probability (RMP)
P = 2pq a heterozygous individual, if the two alleles have frequencies of p and q in a population
P = p2 homozygous for an allele with a frequency of p
Profile Probability = (P1) (P2) ... (Pn)【3】5.群体分析的工具
STRUCTURE
Haplotype frequency estimation used PHASE 2.1.1
ALFRED database (http://alfred.med.yale.edu)参考：
1.https://www.mdpi.com/2073-4425/13/8/1322
State of the Art for Microhaplotypes Genes 2022, 13(8), 1322; https://doi.org/10.3390/genes130813222.Kidd, K.K.; Pakstis, A.J.; Speed, W.C.; Lagace, R.; Chang, J.; Wootton, S.; Ihuegbu, N. Microhaplotype loci are a powerful new type of forensic marker. Forensic Sci. Int. Genet. Suppl. Ser. 2013, 4, e123–e124. [Google Scholar] [CrossRef] kkkidd_ishi25_poster_25sep2014_237327_284_29491_v1.pdf
3.http://www.biology.arizona.edu/human_bio/activities/blackett2/str_frequency.html
4.Current sequencing technology makes microhaplotypes a powerful new type of genetic marker for forensics Forensic Sci Int Genet
. 2014 Sep;12:215-24. doi: 10.1016/j.fsigen.2014.06.014. Epub 2014 Jul 1.
5.https://investigativegenetics.biomedcentral.com/articles/10.1186/s13323-014-0018-3 Criteria for selecting microhaplotypes: mixture detection and deconvolution -
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Genetic diversity analysis with
molecular marker data:
Learning module
04_Measures.pdf
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random match probabilities
identity by descent (IBD)
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https://bitbucket.org/rirgabiss/mhinngs/src/master/
MHinNGS is a tool for analysis of microhaplotypes (MHs) in singleend sequencing data obtained through a massive parallel sequencing plattform (MPS). The tool identifies the reads with the MHs and calls the genotypes of the MHs according to the criteria and positions specified in the configuration file. It also searches for additional variants in the region defined by the start and the stop positions specified in the configuration file.
这个软件的输入是参考序列和原始单端测序的fastq 包括了比对过程 依赖的第三方软件包括
python 3.6 including pip
samtools version 1.9
hisat2 version 2.1.0
stringtie version 2.0.3
agrep T.R.E. version 0.8.0
不支持双端序列
