PMID- 9725863
OWN - NLM
STAT- MEDLINE
DCOM- 19981105
LR  - 20210915
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 150
IP  - 1
DP  - 1998 Sep
TI  - Simultaneous estimation of all the parameters of a stepwise mutation model.
PG  - 487-97
AB  - Minisatellite and microsatellite are short tandemly repetitive sequences 
      dispersed in eukaryotic genomes, many of which are highly polymorphic due to copy 
      number variation of the repeats. Because mutation changes copy numbers of the 
      repeat sequences in a generalized stepwise fashion, stepwise mutation models are 
      widely used for studying the dynamics of these loci. We propose a minimum 
      chi-square (MCS) method for simultaneous estimation of all the parameters in a 
      stepwise mutation model and the ancestral allelic type of a sample. The MCS 
      estimator requires knowing the mean number of alleles of a certain size in a 
      sample, which can be estimated using Monte Carlo samples generated by a 
      coalescent algorithm. The method is applied to samples of seven (CA)n repeat loci 
      from eight human populations and one chimpanzee population. The estimated values 
      of parameters suggest that there is a general tendency for microsatellite alleles 
      to expand in size, because (1) each mutation has a slight tendency to cause size 
      increase and (2) the mean size increase is larger than the mean size decrease for 
      a mutation. Our estimates also suggest that most of these CA-repeat loci evolve 
      according to multistep mutation models rather than single-step mutation models. 
      We also introduced several quantities for measuring the quality of the estimation 
      of ancestral allelic type, and it appears that the majority of the estimated 
      ancestral allelic types are reasonably accurate. Implications of our analysis and 
      potential extensions of the method are discussed. SINCE the discovery that a 
      large number of loci with tandemly repeated sequences in human and many eukaryote 
      species are highly polymorphic because of copy number variation of the repeats in 
      different individuals (Jeffreys 1985; Litt and Luty 1989; Weber and May 1989), 
      allele size data from such loci are rapidly becoming the dominant source of 
      genetic markers for genome mapping, forensic testing, and population studies. 
      Loci with repeat sequences longer than 5 bp are generally referred to as 
      minisatellite or variable number tandem repeat loci, and those with repeat 
      sequences between 2 to 5 bp are referred to as microsatellite or short tandem 
      repeat loci (Tautz 1993). Because mutations change the copy number of such loci 
      in a stepwise fashion, rapid accumulation of population samples from 
      minisatellite and microsatellite loci has resurrected the interest of the 
      stepwise mutation model (SMM), which was popular in the 1970s.
FAU - Fu, Y X
AU  - Fu YX
AD  - Human Genetics Center, University of Texas, Houston, Texas 77225, USA. 
      fu@hgc.sph.uth.tmc.edu
FAU - Chakraborty, R
AU  - Chakraborty R
LA  - eng
GR  - GM58545/GM/NIGMS NIH HHS/United States
GR  - R29 GM-50428/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
SB  - IM
MH  - Chi-Square Distribution
MH  - Humans
MH  - *Models, Genetic
MH  - Monte Carlo Method
MH  - *Mutation
MH  - Polymorphism, Genetic
PMC - PMC1460324
EDAT- 1998/09/02 00:00
MHDA- 1998/09/02 00:01
PMCR- 1998/12/01
CRDT- 1998/09/02 00:00
PHST- 1998/09/02 00:00 [pubmed]
PHST- 1998/09/02 00:01 [medline]
PHST- 1998/09/02 00:00 [entrez]
PHST- 1998/12/01 00:00 [pmc-release]
AID - 10.1093/genetics/150.1.487 [doi]
PST - ppublish
SO  - Genetics. 1998 Sep;150(1):487-97. doi: 10.1093/genetics/150.1.487.